Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T15700 | Target Info | |||
| Target Name | Caspase-8 (CASP8) | ||||
| Synonyms | MORT1-associated CED-3 homolog; MCH5; MACH; ICE-like apoptotic protease 5; FLICE; FADD-like ICE; FADD-homologous ICE/CED-3-like protease; CASP-8; CAP4; Apoptotic protease Mch-5; Apoptotic cysteine protease | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | CASP8 | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: DTD | Ligand Info | |||||
| Structure Description | Caspase-3 specific unnatural amino acid-based peptides | PDB:4JJ7 | ||||
| Method | X-ray diffraction | Resolution | 1.18 Å | Mutation | No | [1] |
| PDB Sequence |
DKVYQMKSKP
232 RGYCLIINNH242 NFAKAREKVP252 KLHSIRDRNG262 THLDAGALTT272 TFEELHFEIK 282 PHDDCTVEQI292 YEILKIYQLM302 DHSNMDCFIC312 CILSHGDKGI322 IYGTDGQEAP 332 IYELTSQFTG342 LKCPSLAGKP352 KVFFIQACQG362 DNYQKGIPVE372 TDTRYIPDEA 397 DFLLGMATVN407 NCVSYRNPAE417 GTWYIQSLCQ427 SLRERCPRGD437 DILTILTEVN 447 YEVSNKDDKK457 NMGKQMPQPT467 FTLRKKLVFP477 S
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: (3S)-3-amino-5-[(2,6-dimethylbenzoyl)oxy]-4-oxopentanoic acid | Ligand Info | |||||
| Structure Description | Caspase-3 specific unnatural amino acid-based peptides | PDB:4JJ7 | ||||
| Method | X-ray diffraction | Resolution | 1.18 Å | Mutation | No | [1] |
| PDB Sequence |
DKVYQMKSKP
232 RGYCLIINNH242 NFAKAREKVP252 KLHSIRDRNG262 THLDAGALTT272 TFEELHFEIK 282 PHDDCTVEQI292 YEILKIYQLM302 DHSNMDCFIC312 CILSHGDKGI322 IYGTDGQEAP 332 IYELTSQFTG342 LKCPSLAGKP352 KVFFIQACQG362 DNYQKGIPVE372 TDTRYIPDEA 397 DFLLGMATVN407 NCVSYRNPAE417 GTWYIQSLCQ427 SLRERCPRGD437 DILTILTEVN 447 YEVSNKDDKK457 NMGKQMPQPT467 FTLRKKLVFP477 S
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: (S)-3-Amino-5-methyl-hexanoic acid | Ligand Info | |||||
| Structure Description | Caspase-3 specific unnatural amino acid-based peptides | PDB:4JJ7 | ||||
| Method | X-ray diffraction | Resolution | 1.18 Å | Mutation | No | [1] |
| PDB Sequence |
DKVYQMKSKP
232 RGYCLIINNH242 NFAKAREKVP252 KLHSIRDRNG262 THLDAGALTT272 TFEELHFEIK 282 PHDDCTVEQI292 YEILKIYQLM302 DHSNMDCFIC312 CILSHGDKGI322 IYGTDGQEAP 332 IYELTSQFTG342 LKCPSLAGKP352 KVFFIQACQG362 DNYQKGIPVE372 TDTRYIPDEA 397 DFLLGMATVN407 NCVSYRNPAE417 GTWYIQSLCQ427 SLRERCPRGD437 DILTILTEVN 447 YEVSNKDDKK457 NMGKQMPQPT467 FTLRKKLVFP477 S
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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 .B3L or .B3L2 or .B3L3 or :3B3L;style chemicals stick;color identity;select .A:411 or .A:412 or .A:413 or .A:414 or .A:415 or .A:455 or .A:457 or .A:458; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 3-(3-Pyridyl)-L-alanine | Ligand Info | |||||
| Structure Description | Caspase-3 specific unnatural amino acid-based peptides | PDB:4JJ7 | ||||
| Method | X-ray diffraction | Resolution | 1.18 Å | Mutation | No | [1] |
| PDB Sequence |
DKVYQMKSKP
232 RGYCLIINNH242 NFAKAREKVP252 KLHSIRDRNG262 THLDAGALTT272 TFEELHFEIK 282 PHDDCTVEQI292 YEILKIYQLM302 DHSNMDCFIC312 CILSHGDKGI322 IYGTDGQEAP 332 IYELTSQFTG342 LKCPSLAGKP352 KVFFIQACQG362 DNYQKGIPVE372 TDTRYIPDEA 397 DFLLGMATVN407 NCVSYRNPAE417 GTWYIQSLCQ427 SLRERCPRGD437 DILTILTEVN 447 YEVSNKDDKK457 NMGKQMPQPT467 FTLRKKLVFP477 S
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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 .1MH or .1MH2 or .1MH3 or :31MH;style chemicals stick;color identity;select .A:258 or .A:261 or .A:413 or .A:415; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 5-Methyl-L-norleucine | Ligand Info | |||||
| Structure Description | Caspase-3 specific unnatural amino acid-based peptides | PDB:4JJ7 | ||||
| Method | X-ray diffraction | Resolution | 1.18 Å | Mutation | No | [1] |
| PDB Sequence |
DKVYQMKSKP
232 RGYCLIINNH242 NFAKAREKVP252 KLHSIRDRNG262 THLDAGALTT272 TFEELHFEIK 282 PHDDCTVEQI292 YEILKIYQLM302 DHSNMDCFIC312 CILSHGDKGI322 IYGTDGQEAP 332 IYELTSQFTG342 LKCPSLAGKP352 KVFFIQACQG362 DNYQKGIPVE372 TDTRYIPDEA 397 DFLLGMATVN407 NCVSYRNPAE417 GTWYIQSLCQ427 SLRERCPRGD437 DILTILTEVN 447 YEVSNKDDKK457 NMGKQMPQPT467 FTLRKKLVFP477 S
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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 .HLX or .HLX2 or .HLX3 or :3HLX;style chemicals stick;color identity;select .A:317 or .A:360 or .A:365 or .A:410 or .A:411 or .A:412 or .A:413; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: D-beta-homoserine | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-8 WITH THE TETRAPEPTIDE INHIBITOR ACE-IETD-ALDEHYDE | PDB:1QTN | ||||
| Method | X-ray diffraction | Resolution | 1.20 Å | Mutation | No | [2] |
| PDB Sequence |
> Chain A
DKVYQMKSKP 232 RGYCLIINNH242 NFAKAREKVP252 KLHSIRDRNG262 THLDAGALTT272 TFEELHFEIK 282 PHDDCTVEQI292 YEILKIYQLM302 DHSNMDCFIC312 CILSHGDKGI322 IYGTDGQEAP 332 IYELTSQFTG342 LKCPSLAGKP352 KVFFIQACQG362 DNYQKGIPVE372 TD > Chain B TRYIPDEADF 399 LLGMATVNNC409 VSYRNPAEGT419 WYIQSLCQSL429 RERCPRGDDI439 LTILTEVNYE 449 VSNKDDKKNM459 GKQMPQPTFT469 LRKKLVFPSD479
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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 .ASJ or .ASJ2 or .ASJ3 or :3ASJ;style chemicals stick;color identity;select .A:260 or .A:316 or .A:317 or .A:318 or .A:358 or .A:359 or .A:360 or .B:411 or .B:412 or .B:413 or .B:419; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (3S)-3-({[(5S)-2-{2-[(1H-benzimidazol-5-ylcarbonyl)amino]ethyl}-7-(cyclohexylmethyl)-1,3-dioxo-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]carbonyl}amino)-4-oxopentanoic acid | Ligand Info | |||||
| Structure Description | Caspase 8 bound to a covalent inhibitor | PDB:3KJN | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [3] |
| PDB Sequence |
> Chain A
DKVYQMKSKP 232 RGYCLIINNH242 NFAKAREKVP252 KLHSIRDRNG262 THLDAGALTT272 TFEELHFEIK 282 PHDDCTVEQI292 YEILKIYQLM302 DHSNMDCFIC312 CILSHGDKGI322 IYGTDGQEAP 332 IYELTSQFTG342 LKCPSLAGKP352 KVFFIQACQG362 DNYQKGIPVE372 TD > Chain B TRYIPDEADF 399 LLGMATVNNC409 VSYRNPAEGT419 WYIQSLCQSL429 RERCPRGDDI439 LTILTEVNYE 449 VSNKDDKKNM459 GKQMPQPTFT469 LRKKLVFPSD479
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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 .B93 or .B932 or .B933 or :3B93;style chemicals stick;color identity;select .A:258 or .A:260 or .A:316 or .A:317 or .A:318 or .A:358 or .A:359 or .A:360 or .A:363 or .A:365 or .B:410 or .B:411 or .B:412 or .B:413 or .B:414 or .B:415 or .B:419 or .B:420; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ARG258[A]
4.196
ARG260[A]
2.904
SER316[A]
3.806
HIS317[A]
3.207
GLY318[A]
3.164
GLN358[A]
2.690
ALA359[A]
4.013
CYS360[A]
1.815
ASP363[A]
4.214
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| Ligand Name: (3S)-3-({[(5S,8R)-2-(3-carboxypropyl)-8-(2-{[(4-chlorophenyl)acetyl]amino}ethyl)-1,3-dioxo-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]carbonyl}amino)-4-oxopentanoic acid | Ligand Info | |||||
| Structure Description | Caspase 8 with covalent inhibitor | PDB:3KJQ | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [3] |
| PDB Sequence |
> Chain A
DKVYQMKSKP 232 RGYCLIINNH242 NFAKAREKVP252 KLHSIRDRNG262 THLDAGALTT272 TFEELHFEIK 282 PHDDCTVEQI292 YEILKIYQLM302 DHSNMDCFIC312 CILSHGDKGI322 IYGTDGQEAP 332 IYELTSQFTG342 LKCPSLAGKP352 KVFFIQACQG362 DNYQKGIPVE372 TD > Chain B TRYIPDEADF 399 LLGMATVNNC409 VSYRNPAEGT419 WYIQSLCQSL429 RERCPRGDDI439 LTILTEVNYE 449 VSNKDDKKNM459 GKQMPQPTFT469 LRKKLVFPSD479
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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 .B94 or .B942 or .B943 or :3B94;style chemicals stick;color identity;select .A:258 or .A:259 or .A:260 or .A:261 or .A:316 or .A:317 or .A:318 or .A:334 or .A:335 or .A:337 or .A:338 or .A:341 or .A:358 or .A:359 or .A:360 or .A:365 or .B:396 or .B:399 or .B:400 or .B:401 or .B:410 or .B:411 or .B:412 or .B:413 or .B:415 or .B:419 or .B:458 or .B:467 or .B:468 or .B:469; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ARG258[A]
2.839
ASP259[A]
3.780
ARG260[A]
2.845
ASN261[A]
4.204
SER316[A]
3.832
HIS317[A]
3.155
GLY318[A]
3.086
TYR334[A]
3.530
GLU335[A]
4.205
THR337[A]
2.530
SER338[A]
2.941
THR341[A]
4.470
GLN358[A]
2.760
ALA359[A]
4.014
CYS360[A]
1.814
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| Ligand Name: Benzyl chloroformate | Ligand Info | |||||
| Structure Description | Crystal structure of caspase-8 in complex with aza-peptide Michael acceptor inhibitor | PDB:2C2Z | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [4] |
| PDB Sequence |
TRYIPDEADF
399 LLGMATVNNC409 VSYRNPAEGT419 WYIQSLCQSL429 RERCPRGDDI439 LTILTEVNYE 449 VSNKDDKKNM459 GKQMPQPTFT469 LRKKLVFPSD479
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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 .PHQ or .PHQ2 or .PHQ3 or :3PHQ;style chemicals stick;color identity;select .B:413 or .B:414 or .B:415 or .B:416; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: {1-[4-(3,4-Dihydroquinolin-1(2H)-YL)-4-oxobutanoyl]hydrazino}acetic acid | Ligand Info | |||||
| Structure Description | Crystal structure of caspase-8 in complex with aza-peptide Michael acceptor inhibitor | PDB:2C2Z | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [4] |
| PDB Sequence |
> Chain A
DKVYQMKSKP 232 RGYCLIINNH242 NFAKAREKVP252 KLHSIRDRNG262 THLDAGALTT272 TFEELHFEIK 282 PHDDCTVEQI292 YEILKIYQLM302 DHSNMDCFIC312 CILSHGDKGI322 IYGTDGQEAP 332 IYELTSQFTG342 LKCPSLAGKP352 KVFFIQACQG362 DNYQKGIPVE372 > Chain B TRYIPDEADF 399 LLGMATVNNC409 VSYRNPAEGT419 WYIQSLCQSL429 RERCPRGDDI439 LTILTEVNYE 449 VSNKDDKKNM459 GKQMPQPTFT469 LRKKLVFPSD479
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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 .MX5 or .MX52 or .MX53 or :3MX5;style chemicals stick;color identity;select .A:253 or .A:254 or .A:256 or .A:257 or .A:258 or .A:260 or .A:316 or .A:317 or .A:318 or .A:324 or .A:358 or .A:359 or .A:360 or .B:411 or .B:412 or .B:413 or .B:419; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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LYS253[A]
4.136
LEU254[A]
3.511
SER256[A]
3.961
ILE257[A]
3.787
ARG258[A]
4.812
ARG260[A]
2.801
SER316[A]
3.464
HIS317[A]
3.109
GLY318[A]
2.978
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Selective detection of caspase-3 versus caspase-7 using activity-based probes with key unnatural amino acids. ACS Chem Biol. 2013 Jul 19;8(7):1558-66. | ||||
| REF 2 | The atomic-resolution structure of human caspase-8, a key activator of apoptosis. Structure. 1999 Sep 15;7(9):1135-43. | ||||
| REF 3 | Kinetic and structural characterization of caspase-3 and caspase-8 inhibition by a novel class of irreversible inhibitors. Biochim Biophys Acta. 2010 Sep;1804(9):1817-31. | ||||
| REF 4 | Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10. J Med Chem. 2006 Sep 21;49(19):5728-49. | ||||
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