Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T15053 | Target Info | |||
| Target Name | Lactate dehydrogenase A (LDHA) | ||||
| Synonyms | Renal carcinoma antigen NYREN59; Renal carcinoma antigen NY-REN-59; PIG19; Llactate dehydrogenase A chain; LDHM; LDH-M; LDH-A; LDH muscle subunit; L-lactate dehydrogenase A chain; Cell proliferationinducing gene 19 protein; Cell proliferation-inducing gene 19 protein | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | LDHA | ||||
| Biochemical Class | CH-OH donor oxidoreductase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: NADH | Ligand Info | |||||
| Structure Description | Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 29 and NADH | PDB:5W8K | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [1] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEQTPQNK21 ITVVGVGAVG31 MACAISILMK41 DLADELALVD51 VIEDKLKGEM 61 MDLQHGSLFL71 RTPKIVSGKD81 YNVTANSKLV91 IITAGARLNL108 VQRNVNIFKF 118 IIPNVVKYSP128 NCKLLIVSNP138 VDILTYVAWK148 ISGFPKNRVI158 GSGCNLDSAR 168 FRYLMGERLG178 VHPLSCHGWV188 LGEHGDSSVP198 VWSGMNVAGV208 SLKTLHPDLG 218 TDKDKEQWKE228 VHKQVVESAY238 EVIKLKGYTS248 WAIGLSVADL258 AESIMKNLRR 268 VHPVSTMIKG278 LYGIKDDVFL288 SVPCILGQNG298 ISDLVKVTLT308 SEEEARLKKS 318 ADTLWGIQKE328 LQF
|
|||||
|
|
VAL25
3.803
GLY26
3.927
VAL27
4.110
GLY28
3.247
ALA29
3.234
VAL30
2.956
GLY31
4.299
VAL50
4.515
ASP51
2.708
VAL52
3.452
ILE53
3.311
LYS56
2.810
TYR82
4.195
THR94
3.119
ALA95
3.321
GLY96
3.276
ALA97
2.999
|
|||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Nicotinamide-Adenine-Dinucleotide | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor (R)-3-((2-chlorophenyl)thio)-6-(3-((4-fluorophenyl)amino)phenyl)-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one | PDB:6BB0 | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [2] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGALNL108 VQRNVNIFKF 118 IIPNVVKYSP128 NCKLLIVSNP138 VDILTYVAWK148 ISGFPKNRVI158 GSGCNLDSAR 168 FRYLMGERLG178 VHPLSCHGWV188 LGEHGDSSVP198 VWSGMNVAGV208 SLKTLHPDLG 218 TDKDKEQWKE228 VHKQVVESAY238 EVIKLKGYTS248 WAIGLSVADL258 AESIMKNLRR 268 VHPVSTMIKG278 LYGIKDDVFL288 SVPCILGQNG298 ISDLVKVTLT308 SEEEARLKKS 318 ADTLWGIQKE328 LQF
|
|||||
|
|
VAL25
3.842
GLY26
4.148
VAL27
4.038
GLY28
3.361
ALA29
3.245
VAL30
3.011
GLY31
4.311
VAL50
4.547
ASP51
2.555
VAL52
3.690
ILE53
3.366
TYR82
4.254
THR94
3.143
ALA95
3.380
GLY96
3.505
|
|||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Oxamic acid | Ligand Info | |||||
| Structure Description | HUMAN MUSCLE L-LACTATE DEHYDROGENASE M CHAIN, TERNARY COMPLEX WITH NADH AND OXAMATE | PDB:1I10 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [3] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .OXM or .OXM2 or .OXM3 or :3OXM;style chemicals stick;color identity;select .A:99 or .A:105 or .A:137 or .A:164 or .A:168 or .A:192 or .A:237 or .A:241 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 2-{3-(3,4-difluorophenyl)-5-hydroxy-4-[(4-sulfamoylphenyl)methyl]-1H-pyrazol-1-yl}-1,3-thiazole-4-carboxylic acid | Ligand Info | |||||
| Structure Description | Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 29 | PDB:5W8J | ||||
| Method | X-ray diffraction | Resolution | 1.55 Å | Mutation | No | [1] |
| PDB Sequence |
ATLKDQLIYN
10 LLKQTPQNKI22 TVVGVGAVGM32 ACAISILMKD42 LADELALVDV52 IEDKLKGEMM 62 DLQHGSLFLR72 TPKIVSGKDY82 NVTANSKLVI92 ITAGARQQEG102 ESRLNLVQRN 112 VNIFKFIIPN122 VVKYSPNCKL132 LIVSNPVDIL142 TYVAWKISGF152 PKNRVIGSGC 162 NLDSARFRYL172 MGERLGVHPL182 SCHGWVLGEH192 GDSSVPVWSG202 MNVAGVSLKT 212 LHPDLGTDKD222 KEQWKEVHKQ232 VVESAYEVIK242 LKGYTSWAIG252 LSVADLAESI 262 MKNLRRVHPV272 STMIKGLYGI282 KDDVFLSVPC292 ILGQNGISDL302 VKVTLTSEEE 312 ARLKKSADTL322 WGIQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .9Y7 or .9Y72 or .9Y73 or :39Y7;style chemicals stick;color identity;select .A:25 or .A:26 or .A:50 or .A:51 or .A:52 or .A:80 or .A:82 or .A:95 or .A:96 or .A:97 or .A:98 or .A:99 or .A:105 or .A:108 or .A:109 or .A:111 or .A:115 or .A:118 or .A:119 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:164 or .A:168 or .A:191 or .A:192 or .A:193 or .A:194 or .A:237 or .A:241 or .A:247 or .A:322; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
VAL25
3.213
GLY26
3.414
VAL50
3.481
ASP51
3.105
VAL52
3.532
LYS80
3.408
TYR82
2.850
ALA95
3.300
GLY96
3.351
ALA97
3.994
ARG98
4.132
GLN99
2.715
ARG105
4.851
LEU108
3.297
VAL109
4.661
ARG111
4.954
ILE115
3.606
|
|||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 2-[3-(4-fluorophenyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid | Ligand Info | |||||
| Structure Description | Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 11 | PDB:5W8H | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [1] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .9Y1 or .9Y12 or .9Y13 or :39Y1;style chemicals stick;color identity;select .A:25 or .A:26 or .A:50 or .A:51 or .A:52 or .A:82 or .A:95 or .A:99 or .A:105 or .A:108 or .A:109 or .A:114 or .A:115 or .A:118 or .A:119 or .A:137 or .A:138 or .A:164 or .A:168 or .A:192 or .A:193 or .A:194 or .A:237 or .A:238 or .A:241 or .A:247 or .A:251; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
VAL25
3.378
GLY26
3.348
VAL50
3.456
ASP51
2.904
VAL52
3.346
TYR82
3.924
ALA95
3.327
GLN99
3.564
ARG105
3.955
LEU108
3.145
VAL109
4.954
ASN114
4.019
ILE115
3.454
PHE118
3.663
|
|||||
| Ligand Name: 2-[3-(3,4-difluorophenyl)-5-hydroxy-1H-pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid | Ligand Info | |||||
| Structure Description | Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 23 and Zinc | PDB:5W8I | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [1] |
| PDB Sequence |
ATLKDQLIYN
10 LLKQTPQNKI22 TVVGVGAVGM32 ACAISILMKD42 LADELALVDV52 IEDKLKGEMM 62 DLQHGSLFLR72 TPKIVSGKDY82 NVTANSKLVI92 ITAGARQQEG102 ESRLNLVQRN 112 VNIFKFIIPN122 VVKYSPNCKL132 LIVSNPVDIL142 TYVAWKISGF152 PKNRVIGSGC 162 NLDSARFRYL172 MGERLGVHPL182 SCHGWVLGEH192 GDSSVPVWSG202 MNVAGVSLKT 212 LHPDLGTDKD222 KEQWKEVHKQ232 VVESAYEVIK242 LKGYTSWAIG252 LSVADLAESI 262 MKNLRRVHPV272 STMIKGLYGI282 KDDVFLSVPC292 ILGQNGISDL302 VKVTLTSEEE 312 ARLKKSADTL322 WGIQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .9YD or .9YD2 or .9YD3 or :39YD;style chemicals stick;color identity;select .A:99 or .A:104 or .A:105 or .A:108 or .A:137 or .A:138 or .A:164 or .A:168 or .A:192 or .A:193 or .A:237 or .A:241 or .A:247 or .A:251; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: Ldh-IN-1 | Ligand Info | |||||
| Structure Description | Crystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 59 and NADH | PDB:5W8L | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [1] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .9YA or .9YA2 or .9YA3 or :39YA;style chemicals stick;color identity;select .A:105 or .A:106 or .A:108 or .A:109 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:164 or .A:168 or .A:191 or .A:192 or .A:193 or .A:194 or .A:234 or .A:237 or .A:238 or .A:241 or .A:247 or .A:322 or .A:325; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG105
3.548
LEU106
3.784
LEU108
3.956
VAL109
3.216
ASN137
3.205
PRO138
3.227
VAL139
3.385
ASP140
2.695
ILE141
3.069
LEU164
3.662
ARG168
2.743
|
|||||
| Ligand Name: 2-[5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-3-{3-[(5-methylthiophen-2-yl)ethynyl]phenyl}-1H-pyrazol-1-yl]-1,3-thiazole-4-carboxylic acid | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF LDHA IN COMPLEX WITH COMPOUND NCGC00420737-09 AT 2.00 A RESOLUTION | PDB:6Q13 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [4] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .P8V or .P8V2 or .P8V3 or :3P8V;style chemicals stick;color identity;select .A:105 or .A:106 or .A:108 or .A:109 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:164 or .A:168 or .A:191 or .A:192 or .A:193 or .A:194 or .A:234 or .A:237 or .A:238 or .A:241 or .A:247 or .A:322 or .A:325; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG105
3.609
LEU106
3.855
LEU108
3.727
VAL109
3.489
ASN137
3.131
PRO138
3.322
VAL139
3.242
ASP140
2.708
ILE141
2.989
LEU164
3.607
ARG168
2.714
|
|||||
| Ligand Name: (6R)-6-(3-aminophenyl)-3-[(2-chlorophenyl)sulfanyl]-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one | Ligand Info | |||||
| Structure Description | LDHA structure in complex with inhibitor 14 | PDB:6MVA | ||||
| Method | X-ray diffraction | Resolution | 2.02 Å | Mutation | No | [5] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGAEGE103 SRLNLVQRNV 113 NIFKFIIPNV123 VKYSPNCKLL133 IVSNPVDILT143 YVAWKISGFP153 KNRVIGSGCN 163 LDSARFRYLM173 GERLGVHPLS183 CHGWVLGEHG193 DSSVPVWSGM203 NVAGVSLKTL 213 HPDLGTDKDK223 EQWKEVHKQV233 VESAYEVIKL243 KGYTSWAIGL253 SVADLAESIM 263 KNLRRVHPVS273 TMIKGLYGIK283 DDVFLSVPCI293 LGQNGISDLV303 KVTLTSEEEA 313 RLKKSADTLW323 GIQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D4S or .D4S2 or .D4S3 or :3D4S;style chemicals stick;color identity;select .A:30 or .A:137 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 2-{3-[3-(cyclopentylethynyl)-4-fluorophenyl]-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-1H-pyrazol-1-yl}-1,3-thiazole-4-carboxylic acid | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF LDHA IN COMPLEX WITH COMPOUND NCGC00384414-01 AT 2.05 A RESOLUTION | PDB:6Q0D | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [4] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .P8M or .P8M2 or .P8M3 or :3P8M;style chemicals stick;color identity;select .A:105 or .A:106 or .A:108 or .A:109 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:164 or .A:168 or .A:191 or .A:192 or .A:193 or .A:194 or .A:234 or .A:237 or .A:238 or .A:241 or .A:247 or .A:322 or .A:325; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG105
3.692
LEU106
4.343
LEU108
3.462
VAL109
4.215
ASN137
3.364
PRO138
3.288
VAL139
3.277
ASP140
2.764
ILE141
2.928
LEU164
3.743
ARG168
2.804
|
|||||
| Ligand Name: (2~{r})-5-(2-Chlorophenyl)sulfanyl-2-(4-Morpholin-4-Ylphenyl)-4-Oxidanyl-2-Thiophen-3-Yl-1,3-Dihydropyridin-6-One | Ligand Info | |||||
| Structure Description | Lactate dehydrogenase A in complex with a trisubstituted piperidine-2,4-dione inhibitor GNE-140 | PDB:4ZVV | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [6] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GN0 or .GN02 or .GN03 or :3GN0;style chemicals stick;color identity;select .A:98 or .A:99 or .A:137 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 1-hydroxy-N-[3-[(7-nitrodibenzofuran-2-yl)sulfonylamino]phenyl]cyclopropane-1-carboxamide | Ligand Info | |||||
| Structure Description | X-ray Structure of Human LDH-A with an Allosteric Inhibitor (Compound 7) | PDB:6SBV | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [7] |
| PDB Sequence |
ATLKDQLIYN
11 LLKQTPQNKI23 TVVGVGAVGM33 ACAISILMKD43 LADELALVDV53 IEDKLKGEMM 63 DLQHGSLFLR73 TPKIVSGKDY83 NVTANSKLVI93 ITAGARQQEG103 ESRLNLVQRN 113 VNIFKFIIPN123 VVKYSPNCKL133 LIVSNPVDIL143 TYVAWKISGF153 PKNRVIGSGC 163 NLDSARFRYL173 MGERLGVHPL183 SCHGWVLGEH193 GDSSVPVWSG203 MNVAGVSLKT 213 LHPDLGTDKD223 KEQWKEVHKQ233 VVESAYEVIK243 LKGYTSWAIG253 LSVADLAESI 263 MKNLRRVHPV273 STMIKGLYGI283 KDDVFLSVPC293 ILGQNGISDL303 VKVTLTSEEE 313 ARLKKSADTL323 WGIQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .L5K or .L5K2 or .L5K3 or :3L5K;style chemicals stick;color identity;select .A:169 or .A:172 or .A:173 or .A:175 or .A:176 or .A:179 or .A:180 or .A:181 or .A:182 or .A:233 or .A:234 or .A:237; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 4-[[4-[(5-Chloranylthiophen-2-yl)carbonylamino]-1,3-bis(oxidanylidene)isoindol-2-yl]methyl]benzoic acid | Ligand Info | |||||
| Structure Description | X-ray Structure of Human LDHA with an Allosteric Inhibitor (Compound 3) | PDB:6SBU | ||||
| Method | X-ray diffraction | Resolution | 2.91 Å | Mutation | No | [7] |
| PDB Sequence |
ATLKDQLIYN
11 LLKTPQNKIT24 VVGVGAVGMA34 CAISILMKDL44 ADELALVDVI54 EDKLKGEMMD 64 LQHGSLFLRT74 PKIVSGKDYN84 VTANSKLVII94 TAGARQQEGE104 SRLNLVQRNV 114 NIFKFIIPNV124 VKYSPNCKLL134 IVSNPVDILT144 YVAWKISGFP154 KNRVIGSGCN 164 LDSARFRYLM174 GERLGVHPLS184 CHGWVLGEHG194 DSSVPVWSGM204 NVAGVSLKTL 214 HPDLGTDKDK224 EQWKEVHKQV234 VESAYEVIKL244 KGYTSWAIGL254 SVADLAESIM 264 KNLRRVHPVS274 TMIKGLYGIK284 DDVFLSVPCI294 LGQNGISDLV304 KVTLTSEEEA 314 RLKKSADTLW324 GIQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .L5N or .L5N2 or .L5N3 or :3L5N;style chemicals stick;color identity;select .A:59 or .A:62 or .A:66 or .A:67 or .A:69 or .A:70 or .A:74 or .A:75 or .A:76 or .A:77 or .A:78 or .A:79; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (2r)-2-{[5-Cyano-4-(3,4-Dichlorophenyl)-6-Oxo-1,6-Dihydropyrimidin-2-Yl]sulfanyl}-N-(4-Sulfamoylphenyl)propanamide | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase A in complex with inhibitor compound 22 | PDB:4JNK | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [8] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARSR105 LNLVQRNVNI 115 FKFIIPNVVK125 YSPNCKLLIV135 SNPVDILTYV145 AWKISGFPKN155 RVIGSGCNLD 165 SARFRYLMGE175 RLGVHPLSCH185 GWVLGEHGDS195 SVPVWSGMNV205 AGVSLKTLHP 215 DLGTDKDKEQ225 WKEVHKQVVE235 SAYEVIKLKG245 YTSWAIGLSV255 ADLAESIMKN 265 LRRVHPVSTM275 IKGLYGIKDD285 VFLSVPCILG295 QNGISDLVKV305 TLTSEEEARL 315 KKSADTLWGI325 QKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .ZHK or .ZHK2 or .ZHK3 or :3ZHK;style chemicals stick;color identity;select .A:97 or .A:98 or .A:104 or .A:105 or .A:108 or .A:109 or .A:112 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:191 or .A:192 or .A:193 or .A:194 or .A:234 or .A:237 or .A:238 or .A:241 or .A:322; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ALA97
3.108
ARG98
3.197
SER104
4.401
ARG105
3.133
LEU108
3.028
VAL109
3.840
ASN112
4.692
ASN137
3.571
PRO138
3.304
VAL139
3.338
ASP140
2.862
|
|||||
| Ligand Name: (6S)-3-[(2-chlorophenyl)sulfanyl]-4-hydroxy-6-(2-hydroxyphenyl)-6-phenyl-5,6-dihydro-2H-pyran-2-one | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor (R)-3-((2-chlorophenyl)thio)-6-(3-((4-fluorophenyl)amino)phenyl)-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one | PDB:6BB0 | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [2] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGALNL108 VQRNVNIFKF 118 IIPNVVKYSP128 NCKLLIVSNP138 VDILTYVAWK148 ISGFPKNRVI158 GSGCNLDSAR 168 FRYLMGERLG178 VHPLSCHGWV188 LGEHGDSSVP198 VWSGMNVAGV208 SLKTLHPDLG 218 TDKDKEQWKE228 VHKQVVESAY238 EVIKLKGYTS248 WAIGLSVADL258 AESIMKNLRR 268 VHPVSTMIKG278 LYGIKDDVFL288 SVPCILGQNG298 ISDLVKVTLT308 SEEEARLKKS 318 ADTLWGIQKE328 LQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D3S or .D3S2 or .D3S3 or :3D3S;style chemicals stick;color identity;select .A:137 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: (5s)-2-[(2-Chlorophenyl)sulfanyl]-5-(2,6-Dichlorophenyl)-3-Hydroxycyclohex-2-En-1-One | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase A in complex with substituted 3-Hydroxy-2-mercaptocyclohex-2-enone compound 104 | PDB:4QO8 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [9] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .36U or .36U2 or .36U3 or :336U;style chemicals stick;color identity;select .A:137 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:247; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (6r)-3-[(2-Chlorophenyl)sulfanyl]-4-Hydroxy-6-(3-Hydroxyphenyl)-6-(Thiophen-3-Yl)-5,6-Dihydropyridin-2(1h)-One | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with hydroxylactam inhibitor compound 9: (6R)-3-[(2-chlorophenyl)sulfanyl]-4-hydroxy-6-(3-hydroxyphenyl)-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one | PDB:5IXS | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [10] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQS104 RLNLVQRNVN 114 IFKFIIPNVV124 KYSPNCKLLI134 VSNPVDILTY144 VAWKISGFPK154 NRVIGSGCNL 164 DSARFRYLMG174 ERLGVHPLSC184 HGWVLGEHGD194 SSVPVWSGMN204 VAGVSLKTLH 214 PDLGTDKDKE224 QWKEVHKQVV234 ESAYEVIKLK244 GYTSWAIGLS254 VADLAESIMK 264 NLRRVHPVST274 MIKGLYGIKD284 DVFLSVPCIL294 GQNGISDLVK304 VTLTSEEEAR 314 LKKSADTLWG324 IQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .6EY or .6EY2 or .6EY3 or :36EY;style chemicals stick;color identity;select .A:98 or .A:99 or .A:137 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 1,4,5,6-Tetrahydronicotinamide adenine dinucleotide | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with hydroxylactam inhibitor compound 9: (6R)-3-[(2-chlorophenyl)sulfanyl]-4-hydroxy-6-(3-hydroxyphenyl)-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one | PDB:5IXS | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [10] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQS104 RLNLVQRNVN 114 IFKFIIPNVV124 KYSPNCKLLI134 VSNPVDILTY144 VAWKISGFPK154 NRVIGSGCNL 164 DSARFRYLMG174 ERLGVHPLSC184 HGWVLGEHGD194 SSVPVWSGMN204 VAGVSLKTLH 214 PDLGTDKDKE224 QWKEVHKQVV234 ESAYEVIKLK244 GYTSWAIGLS254 VADLAESIMK 264 NLRRVHPVST274 MIKGLYGIKD284 DVFLSVPCIL294 GQNGISDLVK304 VTLTSEEEAR 314 LKKSADTLWG324 IQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .TXD or .TXD2 or .TXD3 or :3TXD;style chemicals stick;color identity;select .A:25 or .A:26 or .A:27 or .A:28 or .A:29 or .A:30 or .A:31 or .A:50 or .A:51 or .A:52 or .A:53 or .A:82 or .A:94 or .A:95 or .A:96 or .A:97 or .A:98 or .A:112 or .A:115 or .A:119 or .A:135 or .A:136 or .A:137 or .A:139 or .A:160 or .A:161 or .A:164 or .A:165 or .A:192 or .A:246 or .A:247 or .A:251; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
VAL25
3.842
GLY26
4.014
VAL27
3.931
GLY28
3.213
ALA29
3.255
VAL30
2.964
GLY31
4.463
VAL50
4.507
ASP51
2.562
VAL52
3.553
ILE53
3.544
TYR82
4.188
THR94
3.291
ALA95
3.582
GLY96
3.266
ALA97
3.025
|
|||||
| Ligand Name: 3-(5-Amino-6-{[(1r)-1-Phenylethyl]amino}pyrazin-2-Yl)-4-Chlorobenzoic Acid | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase A in complex with a substituted pyrazine inhibitor compound 18 | PDB:4M49 | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [11] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .22Y or .22Y2 or .22Y3 or :322Y;style chemicals stick;color identity;select .A:29 or .A:30 or .A:98 or .A:137 or .A:192 or .A:193 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (6R)-3-[(2-chlorophenyl)sulfanyl]-6-{3-[(4-fluorophenyl)amino]phenyl}-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor (R)-3-((2-chlorophenyl)thio)-6-(3-((4-fluorophenyl)amino)phenyl)-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one | PDB:6BAD | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [12] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D0Y or .D0Y2 or .D0Y3 or :3D0Y;style chemicals stick;color identity;select .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:103 or .A:137 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG98
3.625
GLN99
2.845
GLN100
3.447
GLU101
4.248
GLY102
4.988
GLU103
4.974
ASN137
2.801
LEU164
3.672
ASP165
3.516
ARG168
3.010
HIS192
2.642
|
|||||
| Ligand Name: (1s)-1-Phenylethyl (4-Chloro-3-{[(4s)-4-(2,6-Dichlorophenyl)-2-Hydroxy-6-Oxocyclohex-1-En-1-Yl]sulfanyl}phenyl)acetate | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor compound 31 | PDB:4R68 | ||||
| Method | X-ray diffraction | Resolution | 2.11 Å | Mutation | No | [13] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .W31 or .W312 or .W313 or :3W31;style chemicals stick;color identity;select .A:99 or .A:105 or .A:108 or .A:137 or .A:138 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: Trans-2-[(2-Nitrophenyl)sulfanyl]-5-Phenylcyclohexane-1,3-Dione | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase A in complex with substituted 3-Hydroxy-2-mercaptocyclohex-2-enone compound 7 | PDB:4QO7 | ||||
| Method | X-ray diffraction | Resolution | 2.14 Å | Mutation | No | [9] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .36V or .36V2 or .36V3 or :336V;style chemicals stick;color identity;select .A:137 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:247; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (2R)-5-[(2-chlorophenyl)sulfanyl]-6'-(4-fluorophenoxy)-4-hydroxy-2-(thiophen-3-yl)-2,3-dihydro[2,2'-bipyridin]-6(1H)-one | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor (R)-5-((2-chlorophenyl)thio)-6'-(4-fluorophenoxy)-4-hydroxy-2-(thiophen-3-yl)-2,3-dihydro-[2,2'-bipyridin]-6(1H)-one | PDB:6BB1 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [14] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARNL108 VQRNVNIFKF 118 IIPNVVKYSP128 NCKLLIVSNP138 VDILTYVAWK148 ISGFPKNRVI158 GSGCNLDSAR 168 FRYLMGERLG178 VHPLSCHGWV188 LGEHGDSSVP198 VWSGMNVAGV208 SLKTLHPDLG 218 TDKDKEQWKE228 VHKQVVESAY238 EVIKLKGYTS248 WAIGLSVADL258 AESIMKNLRR 268 VHPVSTMIKG278 LYGIKDDVFL288 SVPCILGQNG298 ISDLVKVTLT308 SEEEARLKKS 318 ADTLWGIQKE328 LQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D3J or .D3J2 or .D3J3 or :3D3J;style chemicals stick;color identity;select .A:98 or .A:137 or .A:138 or .A:139 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (2R)-5-[(2-chlorophenyl)sulfanyl]-6'-[(4-fluorophenyl)amino]-4-hydroxy-2-(thiophen-3-yl)-2,3-dihydro[2,2'-bipyridin]-6(1H)-one | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor (R)-5-((2-chlorophenyl)thio)-6'-((4-fluorophenyl)amino)-4-hydroxy-2-(thiophen-3-yl)-2,3-dihydro-[2,2'-bipyridin]-6(1H)-one | PDB:6BAG | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [15] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGAGES104 RLNLVQRNVN 114 IFKFIIPNVV124 KYSPNCKLLI134 VSNPVDILTY144 VAWKISGFPK154 NRVIGSGCNL 164 DSARFRYLMG174 ERLGVHPLSC184 HGWVLGEHGD194 SSVPVWSGMN204 VAGVSLKTLH 214 PDLGTDKDKE224 QWKEVHKQVV234 ESAYEVIKLK244 GYTSWAIGLS254 VADLAESIMK 264 NLRRVHPVST274 MIKGLYGIKD284 DVFLSVPCIL294 GQNGISDLVK304 VTLTSEEEAR 314 LKKSADTLWG324 IQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D0V or .D0V2 or .D0V3 or :3D0V;style chemicals stick;color identity;select .A:108 or .A:137 or .A:138 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (6R)-3-[(2-chlorophenyl)sulfanyl]-6-{6-[(4-fluorophenyl)amino]pyridin-2-yl}-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor 3-((2-chlorophenyl)thio)-6-(6-((4-fluorophenyl)amino)pyridin-2-yl)-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one | PDB:6BB3 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [16] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .D4A or .D4A2 or .D4A3 or :3D4A;style chemicals stick;color identity;select .A:99 or .A:105 or .A:108 or .A:112 or .A:137 or .A:138 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLN99
3.476
ARG105
3.929
LEU108
3.385
ASN112
4.726
ASN137
2.707
PRO138
3.589
LEU164
3.765
ASP165
3.484
ARG168
2.939
HIS192
2.705
|
|||||
| Ligand Name: Lactic Acid | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor (S)-5-((2-chlorophenyl)thio)-6'-(4-fluorophenoxy)-4-hydroxy-2-(thiophen-3-yl)-2,3-dihydro-[2,2'-bipyridin]-6(1H)-one | PDB:6BB2 | ||||
| Method | X-ray diffraction | Resolution | 2.47 Å | Mutation | No | [17] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .LAC or .LAC2 or .LAC3 or :3LAC;style chemicals stick;color identity;select .A:99 or .A:105 or .A:137 or .A:164 or .A:168 or .A:192 or .A:237 or .A:241 or .A:247; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: CID 131801110 | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with hydroxylactam inhibitor compound 31: (2~{S})-5-(2-chlorophenyl)sulfanyl-2-(4-morpholin-4-ylphenyl)-4-oxidanyl-2-thiophen-3-yl-1,3-dihydropyridin-6-one | PDB:5IXY | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [10] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQQ100 EGESRLNLVQ 110 RNVNIFKFII120 PNVVKYSPNC130 KLLIVSNPVD140 ILTYVAWKIS150 GFPKNRVIGS 160 GCNLDSARFR170 YLMGERLGVH180 PLSCHGWVLG190 EHGDSSVPVW200 SGMNVAGVSL 210 KTLHPDLGTD220 KDKEQWKEVH230 KQVVESAYEV240 IKLKGYTSWA250 IGLSVADLAE 260 SIMKNLRRVH270 PVSTMIKGLY280 GIKDDVFLSV290 PCILGQNGIS300 DLVKVTLTSE 310 EEARLKKSAD320 TLWGIQKELQ330 F
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GN2 or .GN22 or .GN23 or :3GN2;style chemicals stick;color identity;select .A:98 or .A:137 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:245 or .A:246 or .A:247; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (5r)-2-[(2-Chlorophenyl)sulfanyl]-5-[2,6-Dichloro-3-(Tetrahydro-2h-Pyran-4-Ylamino)phenyl]-3-Hydroxycyclohex-2-En-1-One | Ligand Info | |||||
| Structure Description | Lactate Dehydrogenase in complex with inhibitor compound 13 | PDB:4R69 | ||||
| Method | X-ray diffraction | Resolution | 3.19 Å | Mutation | No | [13] |
| PDB Sequence |
ATLKDQLIYN
10 LLKEEQTPQN20 KITVVGVGAV30 GMACAISILM40 KDLADELALV50 DVIEDKLKGE 60 MMDLQHGSLF70 LRTPKIVSGK80 DYNVTANSKL90 VIITAGARQL106 NLVQRNVNIF 116 KFIIPNVVKY126 SPNCKLLIVS136 NPVDILTYVA146 WKISGFPKNR156 VIGSGCNLDS 166 ARFRYLMGER176 LGVHPLSCHG186 WVLGEHGDSS196 VPVWSGMNVA206 GVSLKTLHPD 216 LGTDKDKEQW226 KEVHKQVVES236 AYEVIKLKGY246 TSWAIGLSVA256 DLAESIMKNL 266 RRVHPVSTMI276 KGLYGIKDDV286 FLSVPCILGQ296 NGISDLVKVT306 LTSEEEARLK 316 KSADTLWGIQ326 KELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .W13 or .W132 or .W133 or :3W13;style chemicals stick;color identity;select .A:98 or .A:99 or .A:137 or .A:164 or .A:165 or .A:168 or .A:192 or .A:193 or .A:194 or .A:233 or .A:234 or .A:237 or .A:238 or .A:241 or .A:247; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: {4-[4-({3-[(2-Methyl-1,3-benzothiazol-6-YL)amino]-3-oxopropyl}amino)-4-oxobutyl]benzyl}propanedioic acid | Ligand Info | |||||
| Structure Description | Human LDHA in complex with 2-((4-(4-((3-((2-methyl-1,3-benzothiazol- 6yl)amino)-3-oxo-propyl)amino)-4-oxo-butyl)phenyl)methyl)propanedioic acid | PDB:4AJP | ||||
| Method | X-ray diffraction | Resolution | 2.38 Å | Mutation | No | [18] |
| PDB Sequence |
ATLKDQLIYN
10 LLKQTPQNKI22 TVVGVGAVGM32 ACAISILMKD42 LADELALVDV52 IEDKLKGEMM 62 DLQHGSLFLR72 TPKIVSGKDY82 NVTANSKLVI92 ITAGARQQEG102 ESRLNLVQRN 112 VNIFKFIIPN122 VVKYSPNCKL132 LIVSNPVDIL142 TYVAWKISGF152 PKNRVIGSGC 162 NLDSARFRYL172 MGERLGVHPL182 SCHGWVLGEH192 GDSSVPVWSG202 MNVAGVSLKT 212 LHPDLGTDKD222 KEQWKEVHKQ232 VVESAYEVIK242 LKGYTSWAIG252 LSVADLAESI 262 MKNLRRVHPV272 STMIKGLYGI282 KDDVFLSVPC292 ILGQNGISDL302 VKVTLTSEEE 312 ARLKKSADTL322 WGIQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .88N or .88N2 or .88N3 or :388N;style chemicals stick;color identity;select .A:25 or .A:26 or .A:27 or .A:28 or .A:29 or .A:30 or .A:31 or .A:50 or .A:51 or .A:52 or .A:82 or .A:94 or .A:95 or .A:96 or .A:97 or .A:98 or .A:99 or .A:105 or .A:115 or .A:118 or .A:119 or .A:135 or .A:136 or .A:137 or .A:164 or .A:168 or .A:192 or .A:237 or .A:247 or .A:251; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
VAL25
4.211
GLY26
3.844
VAL27
4.446
GLY28
3.596
ALA29
4.434
VAL30
3.414
GLY31
4.944
VAL50
4.334
ASP51
2.729
VAL52
3.401
TYR82
4.489
THR94
3.193
ALA95
3.570
GLY96
2.884
ALA97
4.659
|
|||||
| Ligand Name: 3-{[7-(2,4-Dimethoxypyrimidin-5-Yl)-3-Sulfamoylquinolin-4-Yl]amino}benzoic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of human muscle L-lactate dehydrogenase in complex with inhibitor 2, 3-{[7-(2,4-dimethoxypyrimidin-5-yl)-3-sulfamoylquinolin-4-yl]amino}benzoic acid | PDB:4QSM | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [19] |
| PDB Sequence |
ATLKDQLIYN
11 LLKEEQTPQN21 KITVVGVGAV31 GMACAISILM41 KDLADELALV51 DVIEDKLKGE 61 MMDLQHGSLF71 LRTPKIVSGK81 DYNVTANSKL91 VIITAGARQQ101 EGESRLNLVQ 111 RNVNIFKFII121 PNVVKYSPNC131 KLLIVSNPVD141 ILTYVAWKIS151 GFPKNRVIGS 161 GCNLDSARFR171 YLMGERLGVH181 PLSCHGWVLG191 EHGDSSVPVW201 SGMNVAGVSL 211 KTLHPDLGTD221 KDKEQWKEVH231 KQVVESAYEV241 IKLKGYTSWA251 IGLSVADLAE 261 SIMKNLRRVH271 PVSTMIKGLY281 GIKDDVFLSV291 PCILGQNGIS301 DLVKVTLTSE 311 EEARLKKSAD321 TLWGIQKELQ331 FH
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .38K or .38K2 or .38K3 or :338K;style chemicals stick;color identity;select .A:26 or .A:27 or .A:28 or .A:51 or .A:52 or .A:53 or .A:54 or .A:83 or .A:95 or .A:96 or .A:97 or .A:98 or .A:99 or .A:112 or .A:115 or .A:116 or .A:119 or .A:120; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 3-{[3-Carbamoyl-7-(2,4-Dimethoxypyrimidin-5-Yl)quinolin-4-Yl]amino}benzoic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of human muscle L-lactate dehydrogenase in complex with inhibitor 1, 3-{[3-CARBAMOYL-7-(2,4-DIMETHOXYPYRIMIDIN-5-YL)QUINOLIN-4-YL]AMINO}BENZOIC ACID | PDB:4QT0 | ||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [19] |
| PDB Sequence |
ATLKDQLIYN
11 LLKEEQTPQN21 KITVVGVGAV31 GMACAISILM41 KDLADELALV51 DVIEDKLKGE 61 MMDLQHGSLF71 LRTPKIVSGK81 DYNVTANSKL91 VIITAGARQQ101 EGESRLNLVQ 111 RNVNIFKFII121 PNVVKYSPNC131 KLLIVSNPVD141 ILTYVAWKIS151 GFPKNRVIGS 161 GCNLDSARFR171 YLMGERLGVH181 PLSCHGWVLG191 EHGDSSVPVW201 SGMNVAGVSL 211 KTLHPDLGTD221 KDKEQWKEVH231 KQVVESAYEV241 IKLKGYTSWA251 IGLSVADLAE 261 SIMKNLRRVH271 PVSTMIKGLY281 GIKDDVFLSV291 PCILGQNGIS301 DLVKVTLTSE 311 EEARLKKSAD321 TLWGIQKELQ331 FH
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .38Q or .38Q2 or .38Q3 or :338Q;style chemicals stick;color identity;select .A:27 or .A:52 or .A:53 or .A:83 or .A:96 or .A:97 or .A:98 or .A:99 or .A:112 or .A:115 or .A:116 or .A:119 or .A:120; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 5-[(5'-{1-(4-carboxy-1,3-thiazol-2-yl)-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-1H-pyrazol-3-yl}-2'-fluoro[1,1'-biphenyl]-4-yl)oxy]-1H-1,2,3-triazole-4-carboxylic acid | Ligand Info | |||||
| Structure Description | Crystal structure of Human Lactate Dehydrogenase A with Inhibitor Compound 15 | PDB:7M2N | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [20] |
| PDB Sequence |
ATLKDQLIYN
10 LLTPQNKITV24 VGVGAVGMAC34 AISILMKDLA44 DELALVDVIE54 DKLKGEMMDL 64 QHGSLFLRTP74 KIVSGKDYNV84 TANSKLVIIT94 AGARQQEGES104 RLNLVQRNVN 114 IFKFIIPNVV124 KYSPNCKLLI134 VSNPVDILTY144 VAWKISGFPK154 NRVIGSGCNL 164 DSARFRYLMG174 ERLGVHPLSC184 HGWVLGEHGD194 SSVPVWSGMN204 VAGVSLKTLH 214 PDLGTDKDKE224 QWKEVHKQVV234 ESAYEVIKLK244 GYTSWAIGLS254 VADLAESIMK 264 NLRRVHPVST274 MIKGLYGIKD284 DVFLSVPCIL294 GQNGISDLVK304 VTLTSEEEAR 314 LKKSADTLWG324 IQKELQF
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .YOJ or .YOJ2 or .YOJ3 or :3YOJ;style chemicals stick;color identity;select .A:105 or .A:106 or .A:108 or .A:109 or .A:137 or .A:138 or .A:139 or .A:140 or .A:141 or .A:164 or .A:168 or .A:191 or .A:192 or .A:193 or .A:194 or .A:234 or .A:237 or .A:238 or .A:241 or .A:247 or .A:321 or .A:322 or .A:325; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG105
3.006
LEU106
4.441
LEU108
3.493
VAL109
3.595
ASN137
3.232
PRO138
3.535
VAL139
3.260
ASP140
2.710
ILE141
3.111
LEU164
3.719
ARG168
2.878
GLU191
2.784
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH). J Med Chem. 2017 Nov 22;60(22):9184-9204. | ||||
| REF 2 | Structure-guided optimization and in vivo activities of hydroxylactone and hydroxylactam Inhibitors of Human Lactate Dehydrogenase | ||||
| REF 3 | Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase. Proteins. 2001 May 1;43(2):175-85. | ||||
| REF 4 | Pyrazole-Based Lactate Dehydrogenase Inhibitors with Optimized Cell Activity and Pharmacokinetic Properties. J Med Chem. 2020 Oct 8;63(19):10984-11011. | ||||
| REF 5 | Structure-based Optimization of Potent, Cell-Active | ||||
| REF 6 | Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition. Nat Chem Biol. 2016 Oct;12(10):779-86. | ||||
| REF 7 | Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A. ACS Omega. 2020 May 27;5(22):13034-13041. | ||||
| REF 8 | Identification of substituted 2-thio-6-oxo-1,6-dihydropyrimidines as inhibitors of human lactate dehydrogenase. Bioorg Med Chem Lett. 2013 Jun 1;23(11):3186-94. | ||||
| REF 9 | Identification of substituted 3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3764-71. | ||||
| REF 10 | Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice. ACS Med Chem Lett. 2016 Aug 26;7(10):896-901. | ||||
| REF 11 | Identification of 2-amino-5-aryl-pyrazines as inhibitors of human lactate dehydrogenase. Bioorg Med Chem Lett. 2013 Oct 15;23(20):5533-9. | ||||
| REF 12 | Structure-guided optimization and in vivo activities of hydroxylactone and hydroxylactam Inhibitors of Human Lactate Dehydrogenase | ||||
| REF 13 | Optimization of 5-(2,6-dichlorophenyl)-3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase. Bioorg Med Chem Lett. 2015 Jan 1;25(1):75-82. | ||||
| REF 14 | Structure-guided optimization and in vivo activities of hydroxylactone and hydroxylactam Inhibitors of Human Lactate Dehydrogenase | ||||
| REF 15 | Structure-guided optimization and in vivo activities of hydroxylactone and hydroxylactam Inhibitors of Human Lactate Dehydrogenase | ||||
| REF 16 | Structure-guided optimization and in vivo activities of hydroxylactone and hydroxylactam Inhibitors of Human Lactate Dehydrogenase | ||||
| REF 17 | Structure-guided optimization and in vivo activities of hydroxylactone and hydroxylactam Inhibitors of Human Lactate Dehydrogenase | ||||
| REF 18 | Design and synthesis of novel lactate dehydrogenase A inhibitors by fragment-based lead generation. J Med Chem. 2012 Apr 12;55(7):3285-306. | ||||
| REF 19 | Structures of lactate dehydrogenase A (LDHA) in apo, ternary and inhibitor-bound forms. Acta Crystallogr D Biol Crystallogr. 2015 Feb;71(Pt 2):185-95. | ||||
| REF 20 | Dual Glycolate Oxidase/Lactate Dehydrogenase A Inhibitors for Primary Hyperoxaluria. doi:10.1021/acsmedchemlett.1c00196. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.