Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T47466 | Target Info | |||
| Target Name | Porphobilinogen deaminase (HMBS) | ||||
| Synonyms | Preuroporphyrinogen synthase; PBGD; Hydroxymethylbilane synthase; HMBS | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | HMBS | ||||
| Biochemical Class | Alkyl aryl transferase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 3-[5-[[3-(2-carboxyethyl)-5-[[3-(2-carboxyethyl)-5-[[3-(2-carboxyethyl)-4-(carboxymethyl)-5-methyl-1H-pyrrol-2-yl]methyl]-4-(carboxymethyl)-1H-pyrrol-2-yl]methyl]-4-(carboxymethyl)-1H-pyrrol-2-yl]methyl]-4-(carboxymethyl)-1H-pyrrol-3-yl]propanoic acid | Ligand Info | |||
| Canonical SMILES | CC1=C(C(=C(N1)CC2=C(C(=C(N2)CC3=C(C(=C(N3)CC4=C(C(=CN4)CCC(=O)O)CC(=O)O)CCC(=O)O)CC(=O)O)CCC(=O)O)CC(=O)O)CCC(=O)O)CC(=O)O | ||||
| InChI | 1S/C40H46N4O16/c1-18-23(10-37(53)54)20(3-7-34(47)48)28(42-18)15-31-26(13-40(59)60)22(5-9-36(51)52)30(44-31)16-32-25(12-39(57)58)21(4-8-35(49)50)29(43-32)14-27-24(11-38(55)56)19(17-41-27)2-6-33(45)46/h17,41-44H,2-16H2,1H3,(H,45,46)(H,47,48)(H,49,50)(H,51,52)(H,53,54)(H,55,56)(H,57,58)(H,59,60) | ||||
| InChIKey | VHZWMEJYGVBAFI-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 137348625 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7CCZ Crystal structure of the ES2 intermediate form of human hydroxymethylbilane synthase | ||||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | No | [1] |
| PDB Sequence |
RVIRVGTRKS
28 QLARIQTDSV38 VATLKASYPG48 LQFEIIAMKS75 LFTKELEHAL85 EKNEVDLVVH 95 SLKDLPTVLP105 PGFTIGAICK115 RENPHDAVVF125 HPKFVGKTLE135 TLPEKSVVGT 145 SSLRRAAQLQ155 RKFPHLEFRS165 IRGNLNTRLR175 KLDEQQEFSA185 IILATAGLQR 195 MGWHNRVGQI205 LHPEECMYAV215 GQGALGVEVR225 AKDQDILDLV235 GVLHDPETLL 245 RCIAERAFLR255 HLEGGCSVPV265 AVHTAMKDGQ275 LYLTGGVWSL285 DGSDSIQETM 295 QATIHVPAQH305 EDGPEDDPQL315 VGITARNIPR325 GPQLAAQNLG335 ISLANLLLSK 345 GAKNILDVAR355 QLN
|
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|
|
LEU30
4.483
GLN34
4.073
SER75
4.523
SER96
2.719
LEU97
4.528
LYS98
2.593
ASP99
2.765
LEU100
3.677
PRO101
3.652
THR102
2.911
VAL103
4.517
THR145
4.778
SER146
3.031
SER147
2.697
ARG149
2.629
ARG150
2.970
ARG173
3.267
|
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| PDB ID: 7CD0 Crystal structure of the 2-iodoporphobilinogen-bound ES2 intermediate form of human hydroxymethylbilane synthase | ||||||
| Method | X-ray diffraction | Resolution | 2.31 Å | Mutation | No | [1] |
| PDB Sequence |
RVIRVGTRKS
28 QLARIQTDSV38 VATLKASYPG48 LQFEIIAMSS75 LFTKELEHAL85 EKNEVDLVVH 95 SLKDLPTVLP105 PGFTIGAICK115 RENPHDAVVF125 HPKFVGKTLE135 TLPEKSVVGT 145 SSLRRAAQLQ155 RKFPHLEFRS165 IRGNLNTRLR175 KLDEQQEFSA185 IILATAGLQR 195 MGWHNRVGQI205 LHPEECMYAV215 GQGALGVEVR225 AKDQDILDLV235 GVLHDPETLL 245 RCIAERAFLR255 HLEGGCSVPV265 AVHTAMKDGQ275 LYLTGGVWSL285 DGSDSIQETM 295 QATIHVPAQH305 EDGPEDDPQL315 VGITARNIPR325 GPQLAAQNLG335 ISLANLLLSK 345 GAKNILDVAR355 QLN
|
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|
|
LEU30
4.167
GLN34
3.866
LEU76
4.372
SER96
2.820
LEU97
4.451
LYS98
2.385
ASP99
2.889
LEU100
3.576
PRO101
3.439
THR102
2.739
VAL103
4.415
THR145
4.776
SER146
3.070
SER147
2.844
ARG149
2.585
ARG150
2.986
ARG173
2.967
|
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| PDB ID: 7AAK Human porphobilinogen deaminase R173W mutant crystallized in the ES2 intermediate state | ||||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | Yes | [2] |
| PDB Sequence |
KMRVIRVGTR
26 KSQLARIQTD36 SVVATLKASY46 PGLQFEIIAM56 STTGDKILDT66 ALSKIGEKSL 76 FTKELEHALE86 KNEVDLVVHS96 LKDLPTVLPP106 GFTIGAICKR116 ENPHDAVVFH 126 PKFVGKTLET136 LPEKSVVGTS146 SLRRAAQLQR156 KFPHLEFRSI166 RGNLNTWLRK 176 LDEQQEFSAI186 ILATAGLQRM196 GWHNRVGQIL206 HPEECMYAVG216 QGALGVEVRA 226 KDQDILDLVG236 VLHDPETLLR246 CIAERAFLRH256 LEGGCSVPVA266 VHTAMKDGQL 276 YLTGGVWSLD286 GSDSIQETMQ296 ATIHVPAQHE306 DGPEDDPQLV316 GITARNIPRG 326 PQLAAQNLGI336 SLANLLLSKG346 AKNILDVARQ356 LNDAH
|
|||||
|
|
LEU30
4.547
GLN34
4.241
ILE71
3.762
LYS74
2.970
SER75
3.482
SER96
2.788
LEU97
4.480
LYS98
2.663
ASP99
2.858
LEU100
3.605
PRO101
3.665
THR102
2.746
VAL103
4.304
SER146
4.210
SER147
2.798
ARG149
2.820
ARG150
2.674
|
|||||
| PDB ID: 5M6R Human porphobilinogen deaminase in complex with reaction intermediate | ||||||
| Method | X-ray diffraction | Resolution | 2.73 Å | Mutation | No | [3] |
| PDB Sequence |
MRVIRVGTRK
27 SQLARIQTDS37 VVATLKASYP47 GLQFEIIAMS57 TTGDKILDTA67 LSKIGEKSLF 77 TKELEHALEK87 NEVDLVVHSL97 KDLPTVLPPG107 FTIGAICKRE117 NPHDAVVFHP 127 KFVGKTLETL137 PEKSVVGTSS147 LRRAAQLQRK157 FPHLEFRSIR167 GNLNTRLRKL 177 DEQQEFSAII187 LATAGLQRMG197 WHNRVGQILH207 PEECMYAVGQ217 GALGVEVRAK 227 DQDILDLVGV237 LHDPETLLRC247 IAERAFLRHL257 EGGCSVPVAV267 HTAMKDGQLY 277 LTGGVWSLDG287 SDSIQETMQA297 TIHVPAQHED307 GPEDDPQLVG317 ITARNIPRGP 327 QLAAQNLGIS337 LANLLLSKGA347 KNILDVARQL357
|
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .7J8 or .7J82 or .7J83 or :37J8;style chemicals stick;color identity;select .A:30 or .A:34 or .A:72 or .A:73 or .A:74 or .A:75 or .A:96 or .A:97 or .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:103 or .A:121 or .A:145 or .A:146 or .A:147 or .A:148 or .A:149 or .A:150 or .A:170 or .A:173 or .A:187 or .A:188 or .A:189 or .A:191 or .A:192 or .A:195 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:219 or .A:220 or .A:251 or .A:254 or .A:255 or .A:260 or .A:261 or .A:262; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU30
2.739
GLN34
3.212
GLY72
3.316
GLU73
2.319
LYS74
4.650
SER75
3.164
SER96
2.316
LEU97
4.402
LYS98
1.648
ASP99
1.984
LEU100
2.738
PRO101
2.226
THR102
2.111
VAL103
2.648
ASP121
4.914
THR145
3.742
SER146
2.311
SER147
2.100
LEU148
3.909
ARG149
2.088
ARG150
1.890
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structures of hydroxymethylbilane synthase complexed with a substrate analog: a single substrate-binding site for four consecutive condensation steps. Biochem J. 2021 Mar 12;478(5):1023-1042. | ||||
| REF 2 | Characterization of porphobilinogen deaminase mutants reveals that arginine-173 is crucial for polypyrrole elongation mechanism. iScience. 2021 Feb 6;24(3):102152. | ||||
| REF 3 | Structural basis of pyrrole polymerization in human porphobilinogen deaminase. Biochim Biophys Acta Gen Subj. 2018 Sep;1862(9):1948-1955. | ||||
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