Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T33966 | Target Info | |||
| Target Name | Carboxypeptidase A1 (CPA1) | ||||
| Synonyms | CPA | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | CPA1 | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: (2R)-4-methyl-2-[(1S)-1-sulfanylethyl]pentanoic acid | Ligand Info | |||||
| Structure Description | Crystal structure of the human CARBOXYPEPTIDASE A1 in complex with a thiirane mechanism-based inhibitor | PDB:5OM9 | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [1] |
| PDB Sequence |
KEDFVGHQVL
-84 RISVADEAQV-74 QKVKELEDLE-64 HLQLDFWRGP-54 AHPGSPIDVR-44 VPFPSIQAVK -34 IFLESHGISY-24 ETMIEDVQSL-14 LDEEQEQMFR2 STDTFNYATY12 HTLEEIYDFL 22 DLLVAENPHL32 VSKIQIGNTY42 EGRPIYVLKF52 STGGSKRPAI62 WIDTGIHSRE 72 WVTQASGVWF82 AKKITQDYGQ92 DAAFTAILDT102 LDIFLEIVTN112 PDGFAFTHST 122 NRMWRKTRSH132 TAGSLCIGVD142 PNRNWDAGFG152 LSGASSNPCS162 ETYHGKFANS 172 EVEVKSIVDF182 VKDHGNIKAF192 ISIHSYSQLL202 MYPYGYKTEP212 VPDQDELDQL 222 SKAAVTALAS232 LYGTKFNYGS242 IIKAIYQASG252 STIDWTYSQG262 IKYSFTFELR 272 DTGRYGFLLP282 ASQIIPTAKE292 TWLALLTIME302 HTLNHP
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| Ligand Name: Octane-1,3,5,7-Tetracarboxylic Acid | Ligand Info | |||||
| Structure Description | Crystal Structure of Human Carboxypeptidase A1 | PDB:2V77 | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [2] |
| PDB Sequence |
ARSTDTFNYA
10 TYHTLEEIYD20 FLDLLVAENP30 HLVSKIQIGN40 TYEGRPIYVL50 KFSTGGSKRP 60 AIWIDTGIHS70 REWVTQASGV80 WFAKKITQDY90 GQDAAFTAIL100 DTLDIFLEIV 110 TNPDGFAFTH120 STNRMWRKTR130 SHTAGSLCIG140 VDPNRNWDAG150 FGLSGASSNP 160 CSETYHGKFA170 NSEVEVKSIV180 DFVKDHGNIK190 AFISIHSYSQ200 LLMYPYGYKT 210 EPVPDQDELD220 QLSKAAVTAL230 ASLYGTKFNY240 GSIIKAIYQA250 SGSTIDWTYS 260 QGIKYSFTFE270 LRDTGRYGFL280 LPASQIIPTA290 KETWLALLTI300 MEHTLNHP |
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| Ligand Name: (2s)-2-{[(R)-{(1r)-1-[(N-Acetyl-L-Leucyl)amino]ethyl}(Hydroxy)phosphoryl]methyl}-4-Phenylbutanoic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of the human CARBOXYPEPTIDASE A1 in complex with the PHOSPHINIC INHIBITOR Acetyl-Leu-Ala-Y(PO2CH2)-homoPhe-OH | PDB:4UEE | ||||
| Method | X-ray diffraction | Resolution | 2.27 Å | Mutation | No | [3] |
| PDB Sequence |
RSTDTFNYAT
11 YHTLEEIYDF21 LDLLVAENPH31 LVSKIQIGNT41 YEGRPIYVLK51 FSTGGSKRPA 61 IWIDTGIHSR71 EWVTQASGVW81 FAKKITQDYG91 QDAAFTAILD101 TLDIFLEIVT 111 NPDGFAFTHS121 TNRMWRKTRS131 HTAGSLCIGV141 DPNRNWDAGF151 GLSGASSNPC 161 SETYHGKFAN171 SEVEVKSIVD181 FVKDHGNIKA191 FISIHSYSQL201 LMYPYGYKTE 211 PVPDQDELDQ221 LSKAAVTALA231 SLYGTKFNYG241 SIIKAIYQAS251 GSTIDWTYSQ 261 GIKYSFTFEL271 RDTGRYGFLL281 PASQIIPTAK291 ETWLALLTIM301 EHTLNHP |
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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 .LA9 or .LA92 or .LA93 or :3LA9;style chemicals stick;color identity;select .A:69 or .A:71 or .A:72 or .A:127 or .A:142 or .A:144 or .A:145 or .A:163 or .A:164 or .A:194 or .A:196 or .A:197 or .A:198 or .A:199 or .A:203 or .A:243 or .A:247 or .A:248 or .A:250 or .A:253 or .A:254 or .A:255 or .A:268 or .A:270 or .A:279; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
HIS69
3.121
ARG71
2.812
GLU72
2.990
ARG127
2.815
ASP142
4.597
ASN144
2.886
ARG145
2.660
GLU163
3.818
THR164
3.848
SER194
4.952
HIS196
2.969
SER197
3.749
TYR198
3.228
|
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| Ligand Name: (2s)-3-[(R)-{(1r)-1-[(N-Acetyl-L-Leucyl)amino]-2-Phenylethyl}(Hydroxy)phosphoryl]-2-Benzylpropanoic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of the human CARBOXYPEPTIDASE A1 in complex with the PHOSPHINIC INHIBITOR Acetyl-Leu-Phe-Y(PO2CH2)-Phe-OH | PDB:4UEZ | ||||
| Method | X-ray diffraction | Resolution | 2.29 Å | Mutation | No | [4] |
| PDB Sequence |
STDTFNYATY
122 HTLEEIYDFL132 DLLVAENPHL142 VSKIQIGNTY152 EGRPIYVLKF162 STGGSKRPAI 172 WIDTGIHSRE182 WVTQASGVWF192 AKKITQDYGQ202 DAAFTAILDT212 LDIFLEIVTN 222 PDGFAFTHST232 NRMWRKTRSH242 TAGSLCIGVD252 PNRNWDAGFG262 LSGASSNPCS 272 ETYHGKFANS282 EVEVKSIVDF292 VKDHGNIKAF302 ISIHSYSQLL312 MYPYGYKTEP 322 VPDQDELDQL332 SKAAVTALAS342 LYGTKFNYGS352 IIKAIYQASG362 STIDWTYSQG 372 IKYSFTFELR382 DTGRYGFLLP392 ASQIIPTAKE402 TWLALLTIME412 HTLNHP |
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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 .LFF or .LFF2 or .LFF3 or :3LFF;style chemicals stick;color identity;select .A:179 or .A:181 or .A:182 or .A:237 or .A:252 or .A:254 or .A:255 or .A:273 or .A:274 or .A:306 or .A:307 or .A:308 or .A:309 or .A:313 or .A:353 or .A:357 or .A:358 or .A:360 or .A:363 or .A:364 or .A:365 or .A:378 or .A:380 or .A:389; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
HIS179
3.030
ARG181
2.812
GLU182
2.992
ARG237
2.689
ASP252
4.788
ASN254
2.931
ARG255
2.770
GLU273
3.379
THR274
3.743
HIS306
3.028
SER307
3.308
TYR308
3.365
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| Ligand Name: (2s)-2-{[(S)-{(1r)-1-[(N-Acetyl-L-Tyrosyl)amino]ethyl}(Hydroxy)phosphoryl]methyl}-4-Phenylbutanoic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of the human CARBOXYPEPTIDASE A1 in complex with the PHOSPHINIC INHIBITOR Acetyl-Tyr-Ala-Y(PO2CH2)-homoPhe-OH | PDB:6I6Z | ||||
| Method | X-ray diffraction | Resolution | 1.72 Å | Mutation | No | [5] |
| PDB Sequence |
STDTFNYATY
122 HTLEEIYDFL132 DLLVAENPHL142 VSKIQIGNTY152 EGRPIYVLKF162 STGGSKRPAI 172 WIDTGIHSRE182 WVTQASGVWF192 AKKITQDYGQ202 DAAFTAILDT212 LDIFLEIVTN 222 PDGFAFTHST232 NRMWRKTRSH242 TAGSLCIGVD252 PNRNWDAGFG262 LSGASSNPCS 272 ETYHGKFANS282 EVEVKSIVDF292 VKDHGNIKAF302 ISIHSYSQLL312 MYPYGYKTEP 322 VPDQDELDQL332 SKAAVTALAS342 LYGTKFNYGS352 IIKAIYQASG362 STIDWTYSQG 372 IKYSFTFELR382 DTGRYGFLLP392 ASQIIPTAKE402 TWLALLTIME412 HTLNHP |
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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 .TJE or .TJE2 or .TJE3 or :3TJE;style chemicals stick;color identity;select .A:179 or .A:181 or .A:182 or .A:237 or .A:252 or .A:254 or .A:255 or .A:273 or .A:274 or .A:304 or .A:306 or .A:307 or .A:308 or .A:309 or .A:313 or .A:353 or .A:357 or .A:358 or .A:360 or .A:363 or .A:364 or .A:365 or .A:378 or .A:380 or .A:389; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
HIS179
3.150
ARG181
2.944
GLU182
3.046
ARG237
2.631
ASP252
4.531
ASN254
2.894
ARG255
2.681
GLU273
3.746
THR274
3.701
SER304
4.292
HIS306
3.012
SER307
3.576
TYR308
3.291
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Discovery of Mechanism-Based Inactivators for Human Pancreatic Carboxypeptidase A from a Focused Synthetic Library. ACS Med Chem Lett. 2017 Sep 22;8(10):1122-1127. | ||||
| REF 2 | Direct interaction between a human digestive protease and the mucoadhesive poly(acrylic acid). Acta Crystallogr D Biol Crystallogr. 2008 Jul;D64(Pt 7):784-91. | ||||
| REF 3 | Crystal Structure of the Human Carboxypeptidase A1 in Complex with Phosphinic Inhibitors | ||||
| REF 4 | Crystal Structure of the Human Carboxypeptidase A1 in Complex with Phosphinic Inhibitors | ||||
| REF 5 | Synthesis and Structural/Functional Characterization of Selective M14 Metallocarboxypeptidase Inhibitors Based on Phosphinic Pseudopeptide Scaffold: Implications on the Design of Specific Optical Probes. J Med Chem. 2019 Feb 28;62(4):1917-1931. | ||||
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