Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T64074 | Target Info | |||
| Target Name | Scavenger decapping enzyme DcpS (DCPS) | ||||
| Synonyms | Scavenger mRNA-decapping enzyme DcpS; Histidine triad protein member5; Hint-related 7meGMP-directed hydrolase; HINT-5; DCS-1; DCPS | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | DCPS | ||||
| Biochemical Class | Acid anhydrides hydrolase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 7-Methyl-Gpppa | Ligand Info | |||||
| Structure Description | Structure of DcpS bound to m7GpppA | PDB:1ST4 | ||||
| Method | X-ray diffraction | Resolution | 2.02 Å | Mutation | Yes | [1] |
| PDB Sequence |
VRLPFSGFRL
49 QKVLRESARD59 KIIFLHGKVN69 EASGDGDGED79 AVVILEKTPF89 QVEQVAQLLT 99 GSPELQLQFS109 NDIYSTYHLF119 PPRQLNDVKT129 TVVYPATEKH139 LQKYLRQDLR 149 LIRETGDDYR159 NITLPHLESQ169 SLSIQWVYNI179 LDKKAEADRI189 VFENPDPSDG 199 FVLIPDLKWN209 QQQLDDLYLI219 AICHRRGIRS229 LRDLTPEHLP239 LLRNILHQGQ 249 EAILQRYRMK259 GDHLRVYLHY269 LPSYYHLNVH279 FTALGFEAPG289 SGVERAHLLA 299 EVIENLECDP309 RHYQQRTLTF319 ALRADDPLLK329 LLQEAQQ
|
|||||
|
|
LEU144
4.152
ARG145
3.107
GLN146
2.894
LEU148
3.899
TRP175
3.153
ILE179
4.163
GLU185
2.663
ARG188
4.221
ILE203
3.743
PRO204
3.163
ASP205
2.684
LEU206
3.594
|
|||||
| Ligand Name: 7-Methyl-guanosine-5'-triphosphate-5'-guanosine | Ligand Info | |||||
| Structure Description | Structure of DcpS bound to m7GpppG | PDB:1ST0 | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [1] |
| PDB Sequence |
VRLPFSGFRL
49 QKVLRESARD59 KIIFLHGKVN69 EASGDGDGED79 AVVILEKTPF89 QVEQVAQLLT 99 GSPELQLQFS109 NDIYSTYHLF119 PPRQLNDVKT129 TVVYPATEKH139 LQKYLRQDLR 149 LIRETGDDYR159 NITLPHLESQ169 SLSIQWVYNI179 LDKKAEADRI189 VFENPDPSDG 199 FVLIPDLKWN209 QQQLDDLYLI219 AICHRRGIRS229 LRDLTPEHLP239 LLRNILHQGQ 249 EAILQRYRMK259 GDHLRVYLHY269 LPSYYHLNVH279 FTALGFEAPG289 SGVERAHLLA 299 EVIENLECDP309 RHYQQRTLTF319 ALRADDPLLK329 LLQEAQQ
|
|||||
|
|
LEU144
4.806
ARG145
3.604
GLN146
4.277
TRP175
3.229
ILE179
4.063
GLU185
2.857
ARG188
3.510
ILE203
3.629
PRO204
3.157
ASP205
2.638
LEU206
3.448
|
|||||
| Ligand Name: 4-{[(2,4-Diaminoquinazolin-5-Yl)oxy]methyl}benzenesulfonic Acid | Ligand Info | |||||
| Structure Description | Dcps in complex with covalent ligand | PDB:4QDV | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [2] |
| PDB Sequence |
VRLPFSGFRL
49 QKVLRESARD59 KIIFLHGKVE78 DAVVILEKTP88 FQVEQVAQLL98 TGSPELQLQF 108 SNIYSTYHLF119 PPRQLNDVKT129 TVVYPATEKH139 LQKYLRQDLR149 LIRETGDDYR 159 NITLPHLESQ169 SLSIQWVYNI179 LDKKAEADRI189 VFENPDPSDG199 FVLIPDLKWN 209 QQQLDDLYLI219 AICHRRGIRS229 LRDLTPEHLP239 LLRNILHQGQ249 EAILQRYRMK 259 GDHLRVYLHY269 LPSYYHLHVH279 FTALGFEAPG289 SGVERAHLLA299 EVIENLECDP 309 RHYQQRTLTF319 ALRADDPLLK329 LLQEAQQ
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .30U or .30U2 or .30U3 or :330U;style chemicals stick;color identity;select .A:63 or .A:83 or .A:130 or .A:132 or .A:139 or .A:143 or .A:175 or .A:179 or .A:185 or .A:188 or .A:203 or .A:204 or .A:205 or .A:206 or .A:207 or .A:219 or .A:273; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 7-Methylguanosine 5'-phosphate | Ligand Info | |||||
| Structure Description | Structure of human Dcps bound to m7GDP | PDB:1XMM | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [3] |
| PDB Sequence |
VRLPFSGFRL
49 QKVLRESARD59 KIIFLHGKVN69 DAVVILEKTP88 FQVEQVAQLL98 TGSPELQLQF 108 SNDIYSTYHL118 FPPRQLNDVK128 TTVVYPATEK138 HLQKYLRQDL148 RLIRETGDDY 158 RNITLPHLES168 QSLSIQWVYN178 ILDKKAEADR188 IVFENPDPSD198 GFVLIPDLKW 208 NQQQLDDLYL218 IAICHRRGIR228 SLRDLTPEHL238 PLLRNILHQG248 QEAILQRYRM 258 KGDHLRVYLH268 YLPSYYHLHV278 HFTALGFEAP288 GSGVERAHLL298 AEVIENLECD 308 PRHYQQRTLT318 FALRADDPLL328 KLLQEAQQ
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .G7M or .G7M2 or .G7M3 or :3G7M;style chemicals stick;color identity;select .B:175 or .B:179 or .B:185 or .B:188 or .B:203 or .B:204 or .B:205 or .B:206 or .B:207 or .B:272 or .B:273; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 5-{[1-(2,3-Dichlorobenzyl)piperidin-4-yl]methoxy}quinazoline-2,4-diamine | Ligand Info | |||||
| Structure Description | Synthetic Gene Encoded DcpS bound to inhibitor DG157493 | PDB:3BL9 | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [4] |
| PDB Sequence |
LPFSGFRLQK
51 VLRESARDKI61 IFLHGKVNEE78 DAVVILEKTP88 FQVEQVAQLL98 TGSPELQLQF 108 SNDIYSTYHL118 FPPRQLNDVK128 TTVVYPATEK138 HLQKYLRQDL148 RLIRETGDDY 158 RNITLPHLES168 QSLSIQWVYN178 ILDKKAEADR188 IVFENPDPSD198 GFVLIPDLKW 208 NQQQLDDLYL218 IAICHRRGIR228 SLRDLTPEHL238 PLLRNILHQG248 QEAILQRYRM 258 KGDHLRVYLH268 YLPSYYHLHV278 HFTALGFEAP288 GSGVERAHLL298 AEVIENLECD 308 PRHYQQRTLT318 FALRADDPLL328 KLLQEA
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .DD2 or .DD22 or .DD23 or :3DD2;style chemicals stick;color identity;select .A:54 or .A:63 or .A:142 or .A:143 or .A:175 or .A:179 or .A:185 or .A:188 or .A:203 or .A:204 or .A:205 or .A:206 or .A:219 or .A:272 or .A:273; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: [(2S,3S,4R,5R)-5-(2-amino-7-methyl-6-oxo-1H-purin-9-ium-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl-[[[(2S,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl-hydroxyphosphoryl]oxy-hydroxyphosphinothioyl]oxyphosphinic acid | Ligand Info | |||||
| Structure Description | Human Decapping Scavenger enzyme (hDcpS) in complex with m7G(5'S)ppSp(5'S)G mRNA 5' cap analog | PDB:5OSY | ||||
| Method | X-ray diffraction | Resolution | 2.06 Å | Mutation | No | [5] |
| PDB Sequence |
SAPVRLPFSG
46 FRLQKVLRES56 ARDKIIFLHG66 KVNEASGDGD76 GEDAVVILEK86 TPFQVEQVAQ 96 LLTGSPELQL106 QFSNDIYSTY116 HLFPPRQLND126 VKTTVVYPAT136 EKHLQKYLRQ 146 DLRLIRETGD156 DYRNITLPHL166 ESQSLSIQWV176 YNILDKKAEA186 DRIVFENPDP 196 SDGFVLIPDL206 KWNQQQLDDL216 YLIAICHRRG226 IRSLRDLTPE236 HLPLLRNILH 246 QGQEAILQRY256 RMKGDHLRVY266 LHYLPSYYHL276 HVHFTALGFE286 APGSGVERAH 296 LLAEVIENLE306 CDPRHYQQRT316 LTFALRADDP326 LLKLLQEAQQ336 |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AJQ or .AJQ2 or .AJQ3 or :3AJQ;style chemicals stick;color identity;select .A:54 or .A:59 or .A:61 or .A:63 or .A:83 or .A:85 or .A:130 or .A:142 or .A:143 or .A:175 or .A:179 or .A:185 or .A:188 or .A:203 or .A:204 or .A:205 or .A:206 or .A:207 or .A:217 or .A:219 or .A:268 or .A:272 or .A:273 or .A:277 or .A:279 or .A:288 or .A:294; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ARG54
2.698
ASP59
2.699
ILE61
3.726
PHE63
3.853
ILE83
4.052
GLU85
3.058
THR130
4.912
LYS142
2.656
TYR143
2.726
TRP175
3.308
ILE179
4.121
GLU185
2.687
ARG188
3.231
ILE203
4.215
|
|||||
| Ligand Name: 5-{[1-(2-Fluorobenzyl)piperidin-4-yl]methoxy}quinazoline-2,4-diamine | Ligand Info | |||||
| Structure Description | Synthetic Gene Encoded DcpS bound to inhibitor DG156844 | PDB:3BL7 | ||||
| Method | X-ray diffraction | Resolution | 2.31 Å | Mutation | No | [4] |
| PDB Sequence |
LPFSGFRLQK
51 VLRESARDKI61 IFLHGKVNEE78 DAVVILEKTP88 FQVEQVAQLL98 TGSPELQLQF 108 SNDIYSTYHL118 FPPRQLNDVK128 TTVVYPATEK138 HLQKYLRQDL148 RLIRETGDDY 158 RNITLPHLES168 QSLSIQWVYN178 ILDKKAEADR188 IVFENPDPSD198 GFVLIPDLKW 208 NQQQLDDLYL218 IAICHRRGIR228 SLRDLTPEHL238 PLLRNILHQG248 QEAILQRYRM 258 KGDHLRVYLH268 YLPSYYHLHV278 HFTALGFEAP288 GSGVERAHLL298 AEVIENLECD 308 PRHYQQRTLT318 FALRADDPLL328 KLLQEA
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .DD1 or .DD12 or .DD13 or :3DD1;style chemicals stick;color identity;select .A:54 or .A:63 or .A:142 or .A:143 or .A:175 or .A:179 or .A:185 or .A:188 or .A:203 or .A:204 or .A:205 or .A:206 or .A:219 or .A:272 or .A:273; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 5-[(1S)-1-(3-chlorophenyl)ethoxy]quinazoline-2,4-diamine | Ligand Info | |||||
| Structure Description | Synthetic Gene Encoded DcpS bound to inhibitor DG153249 | PDB:3BLA | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [4] |
| PDB Sequence |
LPFSGFRLQK
51 VLRESARDKI61 IFLHGKVNEE78 DAVVILEKTP88 FQVEQVAQLL98 TGSPELQLQF 108 SNDIYSTYHL118 FPPRQLNDVK128 TTVVYPATEK138 HLQKYLRQDL148 RLIRETGDDY 158 RNITLPHLES168 QSLSIQWVYN178 ILDKKAEADR188 IVFENPDPSD198 GFVLIPDLKW 208 NQQQLDDLYL218 IAICHRRGIR228 SLRDLTPEHL238 PLLRNILHQG248 QEAILQRYRM 258 KGDHLRVYLH268 YLPSYYHLHV278 HFTALGFEAP288 GSGVERAHLL298 AEVIENLECD 308 PRHYQQRTLT318 FALRADDPLL328 KLLQEA
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .DD3 or .DD32 or .DD33 or :3DD3;style chemicals stick;color identity;select .A:83 or .A:130 or .A:132 or .A:139 or .A:142 or .A:143 or .A:175 or .A:179 or .A:185 or .A:188 or .A:203 or .A:204 or .A:205 or .A:206 or .A:219 or .A:273; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity. Mol Cell. 2004 Apr 9;14(1):67-80. | ||||
| REF 2 | Dcps in complex with covalent ligands targeting Tyrosines | ||||
| REF 3 | Crystal structures of human DcpS in ligand-free and m7GDP-bound forms suggest a dynamic mechanism for scavenger mRNA decapping. J Mol Biol. 2005 Apr 8;347(4):707-18. | ||||
| REF 4 | DcpS as a therapeutic target for spinal muscular atrophy. ACS Chem Biol. 2008 Nov 21;3(11):711-22. | ||||
| REF 5 | 5'-Phosphorothiolate Dinucleotide Cap Analogues: Reagents for Messenger RNA Modification and Potent Small-Molecular Inhibitors of Decapping Enzymes. J Am Chem Soc. 2018 May 9;140(18):5987-5999. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.