Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T70490 | Target Info | |||
| Target Name | Dipeptidyl peptidase I (CTSC) | ||||
| Synonyms | Dipeptidyl transferase; Dipeptidyl peptidase 1; DPPI; DPP-I; Cysteine protease dipeptidyl peptidase I; Cathepsin J; Cathepsin C; CPPI | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | CTSC | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: L-tyrosine | Ligand Info | |||||
| Structure Description | Crystal structure of Cathepsin C in complex with dipeptide substrates | PDB:4OEL | ||||
| Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | Yes | [1] |
| PDB Sequence |
> Chain A
DTPANCTYLD 10 LLGTWVFQVG20 SSGSQRDVNC30 SVMGPQEKKV40 VVYLQKLDTA50 YDDLGNSGHF 60 TIIYNQGFEI70 VLNDYKWFAF80 FKYKEEGSKV90 TTYCNETMTG100 WVHDVLGRNW 110 ACFTGKKVLH206 LPTSWDWRNV216 HGINFVSPVR226 NQASCGSCYS236 FASMGMLEAR 246 IRILTNNSQT256 PILSPQEVVS266 CSQYAQGCEG276 GFPYLIAGKY286 AQDFGLVEEA 296 CFPYTGTDSP306 CKMKEDCFRY316 YSSEYHYVGG326 FYGGCNEALM336 KLELVHHGPM 346 AVAFEVYDDF356 LHYKKGIYHH366 T> Chain B PFNPFELTNH 381 AVLLVGYGTD391 SASGMDYWIV401 KNSWGTGWGE411 NGYFRIRRGT421 DECAIESIAV 431 AATPIPKLE
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| Ligand Name: L-serine | Ligand Info | |||||
| Structure Description | Crystal structure of Cathepsin C in complex with dipeptide substrates | PDB:4OEL | ||||
| Method | X-ray diffraction | Resolution | 1.40 Å | Mutation | Yes | [1] |
| PDB Sequence |
> Chain A
DTPANCTYLD 10 LLGTWVFQVG20 SSGSQRDVNC30 SVMGPQEKKV40 VVYLQKLDTA50 YDDLGNSGHF 60 TIIYNQGFEI70 VLNDYKWFAF80 FKYKEEGSKV90 TTYCNETMTG100 WVHDVLGRNW 110 ACFTGKKVLH206 LPTSWDWRNV216 HGINFVSPVR226 NQASCGSCYS236 FASMGMLEAR 246 IRILTNNSQT256 PILSPQEVVS266 CSQYAQGCEG276 GFPYLIAGKY286 AQDFGLVEEA 296 CFPYTGTDSP306 CKMKEDCFRY316 YSSEYHYVGG326 FYGGCNEALM336 KLELVHHGPM 346 AVAFEVYDDF356 LHYKKGIYHH366 T> Chain B PFNPFELTNH 381 AVLLVGYGTD391 SASGMDYWIV401 KNSWGTGWGE411 NGYFRIRRGT421 DECAIESIAV 431 AATPIPKLE
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| Ligand Name: L-lysine | Ligand Info | |||||
| Structure Description | Crystal structure of Cathepsin C in complex with dipeptide substrates | PDB:4OEM | ||||
| Method | X-ray diffraction | Resolution | 1.52 Å | Mutation | Yes | [1] |
| PDB Sequence |
> Chain A
DTPANCTYLD 10 LLGTWVFQVG20 SSGSQRDVNC30 SVMGPQEKKV40 VVYLQKLDTA50 YDDLGNSGHF 60 TIIYNQGFEI70 VLNDYKWFAF80 FKYKEEGSKV90 TTYCNETMTG100 WVHDVLGRNW 110 ACFTGKKVHL207 PTSWDWRNVH217 GINFVSPVRN227 QASCGSCYSF237 ASMGMLEARI 247 RILTNNSQTP257 ILSPQEVVSC267 SQYAQGCEGG277 FPYLIAGKYA287 QDFGLVEEAC 297 FPYTGTDSPC307 KMKEDCFRYY317 SSEYHYVGGF327 YGGCNEALMK337 LELVHHGPMA 347 VAFEVYDDFL357 HYKKGIYHHT367 > Chain B FNPFELTNHA 382 VLLVGYGTDS392 ASGMDYWIVK402 NSWGTGWGEN412 GYFRIRRGTD422 ECAIESIAVA 432 ATPIPKLE
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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 .LYS or .LYS2 or .LYS3 or :3LYS;style chemicals stick;color identity;select .A:1 or .A:228 or .A:231 or .A:232 or .A:233 or .A:234 or .A:235 or .A:274 or .A:275 or .A:276 or .A:277 or .B:380 or .B:381 or .B:382; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Gly-Phe-DMK | Ligand Info | |||||
| Structure Description | Crystal Structure of human dipeptidyl peptidase I (Cathepsin C) in complex with the inhibitor Gly-Phe-CHN2 | PDB:2DJF | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [2] |
| PDB Sequence |
> Chain A
DTPANCTYLD 10 LLGTWVFQVG20 SSGSQRDVNC30 SVMGPQEKKV40 VVYLQKLDTA50 YDDLGNSGHF 60 TIIYNQGFEI70 VLNDYKWFAF80 FKYKEEGSKV90 TTYCNETMTG100 WVHDVLGRNW 110 ACFTGKKV> Chain B LPTSWDWRNV 216 HGINFVSPVR226 NQASCGSCYS236 FASMGMLEAR246 IRILTNNSQT256 PILSPQEVVS 266 CSQYAQGCEG276 GFPYLIAGKY286 AQDFGLVEEA296 CFPYTGTDSP306 CKMKEDCFRY 316 YSSEYHYVGG326 FYGGCNEALM336 KLELVHHGPM346 AVAFEVYDDF356 LHYKKGIYHH 366 T> Chain C PFNPFELTNH 381 AVLLVGYGTD391 SASGMDYWIV401 KNSWGTGWGE411 NGYFRIRRGT421 DECAIESIAV 431 AATPIPKL
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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 .1ZB or .1ZB2 or .1ZB3 or :31ZB;style chemicals stick;color identity;select .A:1 or .B:228 or .B:231 or .B:232 or .B:233 or .B:234 or .B:235 or .B:274 or .B:275 or .B:276 or .B:277 or .B:278 or .C:380 or .C:381 or .C:382; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2,5-dibromo-N-{(3R,5S)-1-[(Z)-iminomethyl]-5-methylpyrrolidin-3-yl}benzenesulfonamide | Ligand Info | |||||
| Structure Description | Discovery of Novel Cyanamide-Based Inhibitors of Cathepsin C | PDB:3PDF | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [3] |
| PDB Sequence |
DTPANCTYLD
10 LLGTWVFQVG20 SSGSQRDVNC30 SVMGPQEKKV40 VVYLQKLDTA50 YDDLGNSGHF 60 TIIYNQGFEI70 VLNDYKWFAF80 FKYKEEGSKV90 TTYCNETMTG100 WVHDVLGRNW 110 ACFTGKKVFL207 PTSWDWRNVH217 GINFVSPVRN227 QASCGSCYSF237 ASMGMLEARI 247 RILTNNSQTP257 ILSPQEVVSC267 SQYAQGCEGG277 FPYLIAGKYA287 QDFGLVEEAC 297 FPYTGTDSPC307 KMKEDCFRYY317 SSEYHYVGGF327 YGGCNEALMK337 LELVHHGPMA 347 VAFEVYDDFL357 HYKKGIYHHT367 DPFNPFELTN380 HAVLLVGYGT390 DSASGMDYWI 400 VKNSWGTGWG410 ENGYFRIRRG420 TDECAIESIA430 VAATPIPKLE440 N |
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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 .LXV or .LXV2 or .LXV3 or :3LXV;style chemicals stick;color identity;select .A:1 or .A:64 or .A:228 or .A:231 or .A:232 or .A:233 or .A:234 or .A:235 or .A:274 or .A:275 or .A:276 or .A:277 or .A:278 or .A:279 or .A:349 or .A:379 or .A:380 or .A:381 or .A:382 or .A:429; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (2S,4S)-N-[(2S)-1-azanylidene-3-[4-(4-cyanophenyl)phenyl]propan-2-yl]-4-oxidanyl-piperidine-2-carboxamide | Ligand Info | |||||
| Structure Description | Human DPP1 in complex with (2S,4S)-N-((1S)-1-cyano-2-(4-(4- cyanophenyl)phenyl)ethyl)-4-hydroxy-piperidine-2-carboxamide | PDB:4CDF | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [4] |
| PDB Sequence |
> Chain A
DTPANCTYLD 10 LLGTWVFQVG20 SSGSQRDVNC30 SVMGPQEKKV40 VVYLQKLDTA50 YDDLGNSGHF 60 TIIYNQGFEI70 VLNDYKWFAF80 FKYKEEGSKV90 TTYCNETMTG100 WVHDVLGRNW 110 ACFTGKKVGT120 > Chain B HLPTSWDWRN 215 VHGINFVSPV225 RNQASCGSCY235 SFASMGMLEA245 RIRILTNNSQ255 TPILSPQEVV 265 SCSQYAQGCE275 GGFPYLIAGK285 YAQDFGLVEE295 ACFPYTGTDS305 PCKMKEDCFR 315 YYSSEYHYVG325 GFYGGCNEAL335 MKLELVHHGP345 MAVAFEVYDD355 FLHYKKGIYH 365 HT> Chain C PFNPFELTNH 381 AVLLVGYGTD391 SASGMDYWIV401 KNSWGTGWGE411 NGYFRIRRGT421 DECAIESIAV 431 AATPIPKL
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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 .W2C or .W2C2 or .W2C3 or :3W2C;style chemicals stick;color identity;select .A:1 or .A:2 or .A:3 or .A:64 or .B:228 or .B:231 or .B:232 or .B:233 or .B:234 or .B:235 or .B:274 or .B:275 or .B:276 or .B:277 or .B:278 or .B:349 or .C:379 or .C:380 or .C:381 or .C:382; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ASP1[A]
2.843
THR2[A]
3.759
PRO3[A]
3.248
TYR64[A]
4.657
GLN228[B]
3.018
CYS231[B]
4.536
GLY232[B]
3.605
SER233[B]
3.819
CYS234[B]
1.769
TYR235[B]
3.713
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| Ligand Name: (2S)-N-[(2S)-1-AZANYLIDENE-3-[4-(4-CYANOPHENYL)PHENYL]PROPAN-2-YL]PIPERIDINE-2-CARBOXAMIDE | Ligand Info | |||||
| Structure Description | Human DPP1 in complex with (2S)-N-((1S)-1-cyano-2-(4-(4-cyanophenyl) phenyl)ethyl)piperidine-2-carboxamide | PDB:4CDD | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [4] |
| PDB Sequence |
> Chain A
DTPANCTYLD 10 LLGTWVFQVG20 SSGSQRDVNC30 SVMGPQEKKV40 VVYLQKLDTA50 YDDLGNSGHF 60 TIIYNQGFEI70 VLNDYKWFAF80 FKYKEEGSKV90 TTYCNETMTG100 WVHDVLGRNW 110 ACFTGKKV> Chain B HLPTSWDWRN 215 VHGINFVSPV225 RNQASCGSCY235 SFASMGMLEA245 RIRILTNNSQ255 TPILSPQEVV 265 SCSQYAQGCE275 GGFPYLIAGK285 YAQDFGLVEE295 ACFPYTGTDS305 PCKMKEDCFR 315 YYSSEYHYVG325 GFYGGCNEAL335 MKLELVHHGP345 MAVAFEVYDD355 FLHYKKGIYH 365 HT> Chain C PFNPFELTNH 381 AVLLVGYGTD391 SASGMDYWIV401 KNSWGTGWGE411 NGYFRIRRGT421 DECAIESIAV 431 AATPIPKL
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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 .GDI or .GDI2 or .GDI3 or :3GDI;style chemicals stick;color identity;select .A:1 or .A:2 or .A:3 or .A:64 or .B:228 or .B:231 or .B:232 or .B:233 or .B:234 or .B:235 or .B:274 or .B:275 or .B:276 or .B:277 or .B:278 or .B:349 or .C:379 or .C:380 or .C:381 or .C:382; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ASP1[A]
2.641
THR2[A]
3.737
PRO3[A]
3.266
TYR64[A]
4.486
GLN228[B]
3.196
CYS231[B]
4.707
GLY232[B]
3.699
SER233[B]
3.926
CYS234[B]
1.785
TYR235[B]
3.973
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| Ligand Name: (2S)-2-azanyl-N-[(2S)-1-azanylidene-3-(4-phenylphenyl)propan-2-yl]butanamide | Ligand Info | |||||
| Structure Description | Human DPP1 in complex with (2S)-2-amino-N-((1S)-1-cyano-2-(4- phenylphenyl)ethyl)butanamide | PDB:4CDC | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [4] |
| PDB Sequence |
> Chain A
DTPANCTYLD 10 LLGTWVFQVG20 SSGSQRDVNC30 SVMGPQEKKV40 VVYLQKLDTA50 YDDLGNSGHF 60 TIIYNQGFEI70 VLNDYKWFAF80 FKYKVTTYCN95 ETMTGWVHDV105 LGRNWACFTG 115 KKVG> Chain B HLPTSWDWRN 215 VHGINFVSPV225 RNQASCGSCY235 SFASMGMLEA245 RIRILTNNSQ255 TPILSPQEVV 265 SCSQYAQGCE275 GGFPYLIAGK285 YAQDFGLVEE295 ACFPYTGTDS305 PCKMKEDCFR 315 YYSSEYHYVG325 GFYGGCNEAL335 MKLELVHHGP345 MAVAFEVYDD355 FLHYKKGIYH 365 HT> Chain C PFNPFELTNH 381 AVLLVGYGTD391 SASGMDYWIV401 KNSWGTGWGE411 NGYFRIRRGT421 DECAIESIAV 431 AATPIPKL
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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 .6AO or .6AO2 or .6AO3 or :36AO;style chemicals stick;color identity;select .A:1 or .A:2 or .A:3 or .B:228 or .B:231 or .B:232 or .B:233 or .B:234 or .B:235 or .B:275 or .B:276 or .B:277 or .B:278 or .B:279 or .B:349 or .C:379 or .C:380 or .C:381 or .C:382; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ASP1[A]
2.588
THR2[A]
3.922
PRO3[A]
4.663
GLN228[B]
3.374
CYS231[B]
4.921
GLY232[B]
3.865
SER233[B]
4.195
CYS234[B]
1.793
TYR235[B]
3.924
GLU275[B]
3.516
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| Ligand Name: 4-AZANYL-N-[(2S)-1-AZANYLIDENE-3-[4-(4-CYANOPHENYL)PHENYL]PROPAN-2-YL]OXANE-4-CARBOXAMIDE | Ligand Info | |||||
| Structure Description | Human DPP1 in complex with 4-amino-N-((1S)-1-cyano-2-(4-(4- cyanophenyl)phenyl)ethyl)tetrahydropyran-4-carboxamide | PDB:4CDE | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [4] |
| PDB Sequence |
> Chain A
DTPANCTYLD 10 LLGTWVFQVG20 SSGSQRDVNC30 SVMGPQEKKV40 VVYLQKLDTA50 YDDLGNSGHF 60 TIIYNQGFEI70 VLNDYKWFAF80 FKYKEEGSKV90 TTYCNETMTG100 WVHDVLGRNW 110 ACFTGKKV> Chain B HLPTSWDWRN 215 VHGINFVSPV225 RNQASCGSCY235 SFASMGMLEA245 RIRILTNNSQ255 TPILSPQEVV 265 SCSQYAQGCE275 GGFPYLIAGK285 YAQDFGLVEE295 ACFPYTGTDS305 PCKMKEDCFR 315 YYSSEYHYVG325 GFYGGCNEAL335 MKLELVHHGP345 MAVAFEVYDD355 FLHYKKGIYH 365 H> Chain C PFNPFELTNH 381 AVLLVGYGTD391 SASGMDYWIV401 KNSWGTGWGE411 NGYFRIRRGT421 DECAIESIAV 431 AATPIPKL
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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 .U6B or .U6B2 or .U6B3 or :3U6B;style chemicals stick;color identity;select .A:1 or .A:2 or .A:3 or .A:64 or .B:228 or .B:232 or .B:233 or .B:234 or .B:235 or .B:275 or .B:276 or .B:277 or .B:278 or .B:349 or .C:379 or .C:380 or .C:381 or .C:382; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ASP1[A]
2.939
THR2[A]
4.032
PRO3[A]
3.481
TYR64[A]
4.239
GLN228[B]
3.397
GLY232[B]
3.748
SER233[B]
4.545
CYS234[B]
1.771
TYR235[B]
3.636
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | The amino-acid substituents of dipeptide substrates of cathepsin C can determine the rate-limiting steps of catalysis. Biochemistry. 2012 Sep 25;51(38):7551-68. | ||||
| REF 2 | The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. Biochem J. 2007 Feb 1;401(3):645-50. | ||||
| REF 3 | Discovery of Novel Cyanamide-Based Inhibitors of Cathepsin C | ||||
| REF 4 | Cathepsin C inhibitors: property optimization and identification of a clinical candidate. J Med Chem. 2014 Mar 27;57(6):2357-67. | ||||
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