Binding Site Information of Target

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Target General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T98269 Target Info
Target Name Caspase-1 (CASP1)
Synonyms P45; Interleukin-1 beta-converting enzyme; Interleukin-1 beta converting enzyme; Interleukin-1 beta convertase; IL1BCE; IL1BC; IL-1BC; IL-1 beta-converting enzyme; IL-1 beta converting enzyme; ICE; CASP-1
Target Type Clinical trial Target
Gene Name CASP1
Biochemical Class Peptidase
UniProt ID
CASP1_HUMAN
Drug Binding Sites of Target  Top
Ligand Name: (3S)-4-hydroxy-3-[[(2R)-2-[3-methyl-2,6-dioxo-5-[[4-(quinoxalin-2-ylamino)benzoyl]amino]pyrimidin-1-yl]propanoyl]amino]butanoic acid Ligand Info
Structure Description Crystal structure of human Caspase-1 with N-{3-[1-((S)-2-Hydroxy-5-oxo-tetrahydro-furan-3-ylcarbamoyl)-ethyl]-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl}-4-(quinoxalin-2-ylamino)-benzamide PDB:6F6R
Method X-ray diffraction Resolution 1.80 Å Mutation No [1]
PDB Sequence
> Chain A
QDNPAMPTSS
127
GSEGNVKLCS
137
LEEAQRIWKQ
147
KSAEIYPIMD
157
KSSRTRLALI
167

ICNEEFDSIP
177
RRTGAEVDIT
187
GMTMLLQNLG
197
YSVDVKKNLT
207
ASDMTTELEA
217

FAHRPEHKTS
227
DSTFLVFMSH
237
GIREGICGKK
247
HSEQVPDILQ
257
LNAIFNMLNT
267

KNCPSLKDKP
277
KVIIIQACRG
287
DSPGVVWFKD
297

> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Residue
Distance (Å)
ARG179[A]
2.806
SER236[A]
3.822
HIS237[A]
3.989
GLY238[A]
3.914
GLN283[A]
2.752
ALA284[A]
3.756
CYS285[A]
1.752
VAL338[B]
3.967
SER339[B]
2.827
Residue
Distance (Å)
TRP340[B]
3.394
ARG341[B]
2.820
HIS342[B]
3.493
MET345[B]
3.353
GLY346[B]
3.372
SER347[B]
3.606
VAL348[B]
3.595
GLY351[B]
4.652
ARG383[B]
3.439
Ligand Name: (3S)-3-[[(3S,6S,10aS)-6-(isoquinoline-1-carbonylamino)-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-4-hydroxybutanoic acid Ligand Info
Structure Description Crystal structure of human Caspase-1 with (3S,6S,10aS)-N-((2S,3S)-2-hydroxy-5-oxotetrahydrofuran-3-yl)-6-(isoquinoline-1-carboxamido)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide (PGE-3935199) PDB:5MTK
Method X-ray diffraction Resolution 2.53 Å Mutation No [2]
PDB Sequence
> Chain A
GSEGNVKLCS
137
LEEAQRIWSA
150
EIYPIMDKSS
160
RTRLALIICN
170
EEFDSIPRRT
180

GAEVDITGMT
190
MLLQNLGYSV
200
DVKKNLTASD
210
MTTELEAFAH
220
RPEHKTSDST
230

FLVFMSHGIR
240
EGICGKKHSE
250
QVPDILQLNA
260
IFNMLNTKNC
270
PSLKDKPKVI
280

IIQACRGDSP
290
GVVWFK
> Chain B
IKKAHIEKDF
327
IAFCSSTPDN
337
VSWRHPTMGS
347
VFIGRLIEHM
357
QEYACSCDVE
367

EIFRKVRFSF
377
EQPDGRAQMP
387
TTERVTLTRC
397
FYLFPGH
Residue
Distance (Å)
ARG179[A]
2.904
SER236[A]
3.043
HIS237[A]
2.834
GLY238[A]
4.875
GLN283[A]
3.396
ALA284[A]
3.376
CYS285[A]
1.814
VAL338[B]
4.450
Residue
Distance (Å)
SER339[B]
2.789
TRP340[B]
3.489
ARG341[B]
2.781
HIS342[B]
3.442
PRO343[B]
4.374
VAL348[B]
4.057
ARG383[B]
3.454
Ligand Name: 4-Oxo-3-{6-[4-(quinoxalin-2-yloxy)-benzoylamino]-2-thiophen-2-YL-hexanoylamino}-butyric acid Ligand Info
Structure Description Crystal structure of human caspase-1 in complex with 4-oxo-3-{6-[4-(quinoxalin-2-yloxy)-benzoylamino]-2-thiophen-2-yl-hexanoylamino}-butyric acid PDB:1RWX
Method X-ray diffraction Resolution 1.85 Å Mutation No [3]
PDB Sequence
> Chain A
NPAMPTSSGS
129
EGNVKLCSLE
139
EAQRIWKQKS
149
AEIYPIMDKS
159
SRTRLALIIC
169

NEEFDSIPRR
179
TGAEVDITGM
189
TMLLQNLGYS
199
VDVKKNLTAS
209
DMTTELEAFA
219

HRPEHKTSDS
229
TFLVFMSHGI
239
REGICGKKHS
249
EQVPDILQLN
259
AIFNMLNTKN
269

CPSLKDKPKV
279
IIIQACRGDS
289
PGVVWFKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .YBH or .YBH2 or .YBH3 or :3YBH;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:338 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:347 or .B:348 or .B:352 or .B:377 or .B:381 or .B:383 or .B:384 or .B:385; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.754
SER236[A]
4.032
HIS237[A]
2.839
GLY238[A]
3.504
GLN283[A]
2.738
ALA284[A]
4.357
CYS285[A]
1.815
VAL338[B]
3.954
SER339[B]
2.897
TRP340[B]
3.838
ARG341[B]
2.816
Residue
Distance (Å)
HIS342[B]
3.614
PRO343[B]
4.378
SER347[B]
3.988
VAL348[B]
3.717
ARG352[B]
3.490
PHE377[B]
3.989
ASP381[B]
3.643
ARG383[B]
3.417
ALA384[B]
4.998
GLN385[B]
4.494
Ligand Name: Unii-Q257O24H4J Ligand Info
Structure Description Crystal structure of caspase-1 in complex with VX-765 PDB:6PZP
Method X-ray diffraction Resolution 1.94 Å Mutation No [4]
PDB Sequence
> Chain A
PTSSGSEGNV
133
KLCSLEEAQR
143
IWKQKSAEIY
153
PIMDKSSRTR
163
LALIICNEEF
173

DSIPRRTGAE
183
VDITGMTMLL
193
QNLGYSVDVK
203
KNLTASDMTT
213
ELEAFAHRPE
223

HKTSDSTFLV
233
FMSHGIREGI
243
CGKKHSEQVP
253
DILQLNAIFN
263
MLNTKNCPSL
273

KDKPKVIIIQ
283
ACRGDSPGVV
293
WFKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .P7S or .P7S2 or .P7S3 or :3P7S;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:338 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:347 or .B:348 or .B:383; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.655
SER236[A]
4.028
HIS237[A]
3.106
GLY238[A]
3.371
GLN283[A]
2.859
ALA284[A]
4.567
CYS285[A]
1.770
VAL338[B]
3.942
Residue
Distance (Å)
SER339[B]
2.776
TRP340[B]
3.580
ARG341[B]
2.875
HIS342[B]
3.458
PRO343[B]
4.229
SER347[B]
3.913
VAL348[B]
3.254
ARG383[B]
3.296
Ligand Name: 3-{2-Ethyl-6-[4-(quinoxalin-2-ylamino)-benzoylamino]-hexanoylamino}-4-oxo-butyric acid Ligand Info
Structure Description Crystal structure of human caspase-1 in complex with 3-{2-ethyl-6-[4-(quinoxalin-2-ylamino)-benzoylamino]-hexanoylamino}-4-oxo-butyric acid PDB:1RWN
Method X-ray diffraction Resolution 2.00 Å Mutation No [5]
PDB Sequence
> Chain A
TSSGSEGNVK
134
LCSLEEAQRI
144
WKQKSAEIYP
154
IMDKSSRTRL
164
ALIICNEEFD
174

SIPRRTGAEV
184
DITGMTMLLQ
194
NLGYSVDVKK
204
NLTASDMTTE
214
LEAFAHRPEH
224

KTSDSTFLVF
234
MSHGIREGIC
244
GKKHSEQVPD
254
ILQLNAIFNM
264
LNTKNCPSLK
274

DKPKVIIIQA
284
CRGDSPGVVW
294
FKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .4QB or .4QB2 or .4QB3 or :34QB;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:338 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:345 or .B:346 or .B:347 or .B:348 or .B:383; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.701
SER236[A]
3.944
HIS237[A]
2.814
GLY238[A]
3.508
GLN283[A]
2.733
ALA284[A]
4.249
CYS285[A]
1.815
VAL338[B]
3.791
SER339[B]
2.826
Residue
Distance (Å)
TRP340[B]
3.439
ARG341[B]
2.710
HIS342[B]
3.285
PRO343[B]
4.541
MET345[B]
3.695
GLY346[B]
3.297
SER347[B]
3.911
VAL348[B]
3.755
ARG383[B]
3.385
Ligand Name: 4-Oxo-3-{6-[4-(quinoxalin-2-ylamino)-benzoylamino]-2-thiophen-2-YL-hexanoylamino}-pentanoic acid Ligand Info
Structure Description Crystal structure of human caspase-1 in complex with 4-oxo-3-{6-[4-(quinoxalin-2-ylamino)-benzoylamino]-2-thiophen-2-yl-hexanoylamino}-pentanoic acid PDB:1RWO
Method X-ray diffraction Resolution 2.10 Å Mutation No [5]
PDB Sequence
> Chain A
TSSGSEGNVK
134
LCSLEEAQRI
144
WKQKSAEIYP
154
IMDKSSRTRL
164
ALIICNEEFD
174

SIPRRTGAEV
184
DITGMTMLLQ
194
NLGYSVDVKK
204
NLTASDMTTE
214
LEAFAHRPEH
224

KTSDSTFLVF
234
MSHGIREGIC
244
GKKHSEQVPD
254
ILQLNAIFNM
264
LNTKNCPSLK
274

DKPKVIIIQA
284
CRGDSPGVVW
294
FKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BTH or .BTH2 or .BTH3 or :3BTH;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:338 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:345 or .B:346 or .B:347 or .B:348 or .B:351 or .B:383; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.728
SER236[A]
3.818
HIS237[A]
3.210
GLY238[A]
3.059
GLN283[A]
2.725
ALA284[A]
4.143
CYS285[A]
1.613
VAL338[B]
3.728
SER339[B]
3.205
TRP340[B]
3.343
Residue
Distance (Å)
ARG341[B]
2.658
HIS342[B]
3.320
PRO343[B]
4.645
MET345[B]
3.500
GLY346[B]
3.324
SER347[B]
3.838
VAL348[B]
3.565
GLY351[B]
4.773
ARG383[B]
3.479
Ligand Name: 5-[5-(1-Carboxymethyl-2-oxo-propylcarbamoyl)-5-phenyl-pentylsulfamoyl]-2-hydroxy-benzoic acid Ligand Info
Structure Description Crystal structure of human caspase-1 in complex with 5-[5-(1-carboxymethyl-2-oxo-propylcarbamoyl)-5-phenyl-pentylsulfamoyl]-2-hydroxy-benzoic acid PDB:1RWV
Method X-ray diffraction Resolution 2.10 Å Mutation No [6]
PDB Sequence
> Chain A
TSSGSEGNVK
134
LCSLEEAQRI
144
WKQKSAEIYP
154
IMDKSSRTRL
164
ALIICNEEFD
174

SIPRRTGAEV
184
DITGMTMLLQ
194
NLGYSVDVKK
204
NLTASDMTTE
214
LEAFAHRPEH
224

KTSDSTFLVF
234
MSHGIREGIC
244
GKKHSEQVPD
254
ILQLNAIFNM
264
LNTKNCPSLK
274

DKPKVIIIQA
284
CRGDSPGVVW
294
FKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .5PH or .5PH2 or .5PH3 or :35PH;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:338 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:347 or .B:383; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.686
SER236[A]
3.703
HIS237[A]
3.063
GLY238[A]
2.833
GLN283[A]
2.692
ALA284[A]
4.070
CYS285[A]
1.814
VAL338[B]
4.042
Residue
Distance (Å)
SER339[B]
3.048
TRP340[B]
3.758
ARG341[B]
2.681
HIS342[B]
4.014
PRO343[B]
3.312
SER347[B]
3.824
ARG383[B]
2.780
Ligand Name: 3-{6-[(8-Hydroxy-quinoline-2-carbonyl)-amino]-2-thiophen-2-YL-hexanoylamino}-4-oxo-butyri acid Ligand Info
Structure Description Crystal structure of human caspase-1 in complex with 3-{6-[(8-hydroxy-quinoline-2-carbonyl)-amino]-2-thiophen-2-yl-hexanoylamino}-4-oxo-butyric acid PDB:1RWP
Method X-ray diffraction Resolution 2.20 Å Mutation No [5]
PDB Sequence
> Chain A
TSSGSEGNVK
134
LCSLEEAQRI
144
WKQKSAEIYP
154
IMDKSSRTRL
164
ALIICNEEFD
174

SIPRRTGAEV
184
DITGMTMLLQ
194
NLGYSVDVKK
204
NLTASDMTTE
214
LEAFAHRPEH
224

KTSDSTFLVF
234
MSHGIREGIC
244
GKKHSEQVPD
254
ILQLNAIFNM
264
LNTKNCPSLK
274

DKPKVIIIQA
284
CRGDSPGVVW
294
FKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .HQC or .HQC2 or .HQC3 or :3HQC;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:338 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:347 or .B:383; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.626
SER236[A]
4.081
HIS237[A]
2.783
GLY238[A]
3.641
GLN283[A]
2.707
ALA284[A]
4.365
CYS285[A]
1.815
VAL338[B]
3.834
Residue
Distance (Å)
SER339[B]
2.922
TRP340[B]
3.415
ARG341[B]
2.929
HIS342[B]
3.426
PRO343[B]
3.380
SER347[B]
3.808
ARG383[B]
3.451
Ligand Name: 3-(2-Mercapto-acetylamino)-4-oxo-pentanoic acid Ligand Info
Structure Description Crystal structure of human caspase-1 in complex with 3-(2-mercapto-acetylamino)-4-oxo-pentanoic acid PDB:1RWK
Method X-ray diffraction Resolution 2.30 Å Mutation No [5]
PDB Sequence
> Chain A
TSSGSEGNVK
134
LCSLEEAQRI
144
WKQKSAEIYP
154
IMDKSSRTRL
164
ALIICNEEFD
174

SIPRRTGAEV
184
DITGMTMLLQ
194
NLGYSVDVKK
204
NLTASDMTTE
214
LEAFAHRPEH
224

KTSDSTFLVF
234
MSHGIREGIC
244
GKKHSEQVPD
254
ILQLNAIFNM
264
LNTKNCPSLK
274

DKPKVIIIQA
284
CRGDSPGVVW
294
FKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .158 or .1582 or .1583 or :3158;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:338 or .B:339 or .B:340 or .B:341 or .B:347; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.627
SER236[A]
3.949
HIS237[A]
3.118
GLY238[A]
2.987
GLN283[A]
2.675
ALA284[A]
4.109
Residue
Distance (Å)
CYS285[A]
1.611
VAL338[B]
4.990
SER339[B]
2.860
TRP340[B]
3.963
ARG341[B]
2.846
SER347[B]
3.707
Ligand Name: (3S)-4-oxo-3-[[2-[5-[[[4-(quinoxalin-2-ylamino)benzoyl]amino]methyl]thiophen-2-yl]acetyl]amino]pentanoic acid Ligand Info
Structure Description Crystal structure of human caspase-1 in complex with 4-oxo-3-[2-(5-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-thiophen-2-yl)-acetylamino]-pentanoic acid PDB:1RWM
Method X-ray diffraction Resolution 2.70 Å Mutation No [5]
PDB Sequence
> Chain A
TSSGSEGNVK
134
LCSLEEAQRI
144
WKQKSAEIYP
154
IMDKSSRTRL
164
ALIICNEEFD
174

SIPRRTGAEV
184
DITGMTMLLQ
194
NLGYSVDVKK
204
NLTASDMTTE
214
LEAFAHRPEH
224

KTSDSTFLVF
234
MSHGIREGIC
244
GKKHSEQVPD
254
ILQLNAIFNM
264
LNTKNCPSLK
274

DKPKVIIIQA
284
CRGDSPGVVW
294
FKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .Q2Y or .Q2Y2 or .Q2Y3 or :3Q2Y;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:347 or .B:348 or .B:352 or .B:377 or .B:381 or .B:383 or .B:384 or .B:385; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.606
SER236[A]
3.971
HIS237[A]
3.208
GLY238[A]
3.280
GLN283[A]
2.735
ALA284[A]
3.963
CYS285[A]
1.623
SER339[B]
2.982
TRP340[B]
3.934
ARG341[B]
2.867
Residue
Distance (Å)
HIS342[B]
3.250
PRO343[B]
4.792
SER347[B]
4.026
VAL348[B]
3.763
ARG352[B]
3.297
PHE377[B]
3.779
ASP381[B]
4.143
ARG383[B]
3.134
ALA384[B]
4.851
GLN385[B]
4.695
Ligand Name: 4-Oxo-3-[(6-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-pyridine-3-carbonyl)-amino]-butyric acid Ligand Info
Structure Description Crystal structure of human caspase-1 in complex with 4-oxo-3-[(6-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-pyridine-3-carbonyl)-amino]-butyric acid PDB:1RWW
Method X-ray diffraction Resolution 2.80 Å Mutation No [3]
PDB Sequence
> Chain A
MPTSSGSEGN
132
VKLCSLEEAQ
142
RIWKQKSAEI
152
YPIMDKSSRT
162
RLALIICNEE
172

FDSIPRRTGA
182
EVDITGMTML
192
LQNLGYSVDV
202
KKNLTASDMT
212
TELEAFAHRP
222

EHKTSDSTFL
232
VFMSHGIREG
242
ICGKKHSEQV
252
PDILQLNAIF
262
NMLNTKNCPS
272

LKDKPKVIII
282
QACRGDSPGV
292
VWFKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .OQB or .OQB2 or .OQB3 or :3OQB;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:339 or .B:340 or .B:341 or .B:342 or .B:345 or .B:346 or .B:347 or .B:348 or .B:351 or .B:383; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.547
SER236[A]
3.908
HIS237[A]
2.996
GLY238[A]
3.308
GLN283[A]
2.614
ALA284[A]
4.071
CYS285[A]
1.811
SER339[B]
3.013
TRP340[B]
3.579
Residue
Distance (Å)
ARG341[B]
2.620
HIS342[B]
3.356
MET345[B]
3.365
GLY346[B]
3.712
SER347[B]
3.352
VAL348[B]
3.705
GLY351[B]
4.443
ARG383[B]
3.255
Ligand Name: 1-Methyl-3-trifluoromethyl-1H-thieno[2,3-C]pyrazole-5-carboxylic acid (2-mercapto-ethyl)-amide Ligand Info
Structure Description Crystal structure of human caspase-1 (Cys285->Ala, Cys362->Ala, Cys364->Ala, Cys397->Ala) in complex with 1-methyl-3-trifluoromethyl-1H-thieno[2,3-c]pyrazole-5-carboxylic acid (2-mercapto-ethyl)-amide PDB:2FQQ
Method X-ray diffraction Resolution 3.30 Å Mutation Yes [7]
PDB Sequence
> Chain A
EIYPIMDKSS
160
RTRLALIICN
170
EEFDSIPRRT
180
GAEVDITGMT
190
MLLQNLGYSV
200

DVKKNLTASD
210
MTTELEAFAH
220
RPEHKTSDST
230
FLVFMSHGIR
240
EGICGKKHSE
250

QVPDILQLNA
260
IFNMLNTKNC
270
PSLKDKPKVI
280
IIQAARGDSP
290
GVVWFKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYAASADV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
AFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .F1G or .F1G2 or .F1G3 or :3F1G;style chemicals stick;color identity;select .A:258 or .A:282 or .A:286 or .B:331 or .B:333 or .B:388 or .B:390; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU258[A]
3.405
ILE282[A]
4.367
ARG286[A]
3.435
CYS331[B]
1.814
Residue
Distance (Å)
SER333[B]
3.933
THR388[B]
4.704
GLU390[B]
2.739
Ligand Name: (3s)-n-Methanesulfonyl-3-({1-[n-(2-naphtoyl)-l-valyl]-l-prolyl}amino)-4-oxobutanamide Ligand Info
Structure Description CRYSTAL STRUCTURE OF THE COMPLEX OF INTERLEUKIN-1BETA CONVERTING ENZYME (ICE) WITH A PEPTIDE BASED INHIBITOR, (3S )-N-METHANESULFONYL-3-({1-[N-(2-NAPHTOYL)-L-VALYL]-L-PROLYL }AMINO)-4-OXOBUTANAMIDE PDB:1BMQ
Method X-ray diffraction Resolution 2.50 Å Mutation No [8]
PDB Sequence
> Chain A
GNVKLCSLEE
140
AQRIWKQKSA
150
EIYPIMDKSS
160
RTRLALIICN
170
EEFDSIPRRT
180

GAEVDITGMT
190
MLLQNLGYSV
200
DVKKNLTASD
210
MTTELEAFAH
220
RPEHKTSDST
230

FLVFMSHGIR
240
EGICGKKHSE
250
QVPDILQLNA
260
IFNMLNTKNC
270
PSLKDKPKVI
280

IIQACRGDSP
290
GVVWFKD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .MNO or .MNO2 or .MNO3 or :3MNO;style chemicals stick;color identity;select .A:173 or .A:176 or .A:177 or .A:178 or .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:338 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:347 or .B:348 or .B:383; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
PHE173[A]
4.782
ILE176[A]
4.981
PRO177[A]
3.240
ARG178[A]
4.752
ARG179[A]
2.796
SER236[A]
4.445
HIS237[A]
2.754
GLY238[A]
3.585
GLN283[A]
3.710
ALA284[A]
4.031
Residue
Distance (Å)
CYS285[A]
1.754
VAL338[B]
3.783
SER339[B]
2.755
TRP340[B]
3.236
ARG341[B]
2.542
HIS342[B]
4.130
PRO343[B]
3.883
SER347[B]
4.178
VAL348[B]
4.373
ARG383[B]
3.607
Ligand Name: (3s)-4-Hydroxy-3-{[(2s)-4-{[2-(2-Methyl-1h-Benzimidazol-1-Yl)ethyl]amino}-2-(1-Methylethyl)-4-Oxobutanoyl]amino}butanoic Acid Ligand Info
Structure Description Succinic Acid Amides as P2-P3 Replacements for Inhibitors of Interleukin-1beta Converting Enzyme (ICE or Caspase 1) PDB:3NS7
Method X-ray diffraction Resolution 2.60 Å Mutation No [9]
PDB Sequence
> Chain A
CSLEEAQRIW
145
KQKSAEIYPI
155
MDKSSRTRLA
165
LIICNEEFDS
175
IPRRTGAEVD
185

ITGMTMLLQN
195
LGYSVDVKKN
205
LTASDMTTEL
215
EAFAHRPEHK
225
TSDSTFLVFM
235

SHGIREGICG
245
KKHSEQVPDI
255
LQLNAIFNML
265
NTKNCPSLKD
275
KPKVIIIQAC
285

RGDSPGVVWF
295
KD
> Chain B
AIKKAHIEKD
326
FIAFCSSTPD
336
NVSWRHPTMG
346
SVFIGRLIEH
356
MQEYACSCDV
366

EEIFRKVRFS
376
FEQPDGRAQM
386
PTTERVTLTR
396
CFYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .3NS or .3NS2 or .3NS3 or :33NS;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .B:338 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:347 or .B:348 or .B:383; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.810
SER236[A]
3.077
HIS237[A]
2.680
GLY238[A]
4.095
GLN283[A]
2.723
ALA284[A]
3.250
CYS285[A]
1.795
VAL338[B]
3.883
Residue
Distance (Å)
SER339[B]
2.875
TRP340[B]
3.363
ARG341[B]
2.546
HIS342[B]
3.962
PRO343[B]
4.142
SER347[B]
4.493
VAL348[B]
4.214
ARG383[B]
3.236
Ligand Name: (3~{S})-3-[[(3~{S})-2-[(2~{S})-3-methyl-2-(naphthalen-2-ylcarbonylamino)butanoyl]-4-oxidanyl-2-azabicyclo[2.2.2]octan-3-yl]carbonylamino]-4-oxidanyl-butanoic acid Ligand Info
Structure Description Crystal structure of human Caspase-1 with 2-((2-naphthoyl)-L-valyl)-4-hydroxy-N-((3S)-2-hydroxy-5-oxotetrahydrofuran-3-yl)-2-azabicyclo[2.2.2]octane-3-carboxamide (Compound 1) PDB:5MMV
Method X-ray diffraction Resolution 2.15 Å Mutation No [10]
PDB Sequence
> Chain A
GSEGNVKLCS
137
LEEAQRIWSA
150
EIYPIMDKSS
160
RTRLALIICN
170
EEFDSIPRRT
180

GAEVDITGMT
190
MLLQNLGYSV
200
DVKKNLTASD
210
MTTELEAFAH
220
RPEHKTSDST
230

FLVFMSHGIR
240
EGICGKKHSE
250
QVPDILQLNA
260
IFNMLNTKNC
270
PSLKDKPKVI
280

IIQACRGDSP
290
GVVWFK
> Chain B
IKKAHIEKDF
327
IAFCSSTPDN
337
VSWRHPTMGS
347
VFIGRLIEHM
357
QEYACSCDVE
367

EIFRKVRFSF
377
EQPDGRAQMP
387
TTERVTLTRC
397
FYLFPGH
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .WE0 or .WE02 or .WE03 or :3WE0;style chemicals stick;color identity;select .A:179 or .A:236 or .A:237 or .A:238 or .A:283 or .A:284 or .A:285 or .A:288 or .B:338 or .B:339 or .B:340 or .B:341 or .B:342 or .B:343 or .B:347 or .B:348 or .B:383; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
ARG179[A]
2.746
SER236[A]
3.558
HIS237[A]
3.263
GLY238[A]
4.155
GLN283[A]
2.782
ALA284[A]
4.089
CYS285[A]
1.887
ASP288[A]
4.426
VAL338[B]
3.339
Residue
Distance (Å)
SER339[B]
2.772
TRP340[B]
3.606
ARG341[B]
2.752
HIS342[B]
3.541
PRO343[B]
4.456
SER347[B]
4.139
VAL348[B]
4.164
ARG383[B]
3.437
References  Top
REF 1 Rational Drug Design of Topically Administered Caspase 1 Inhibitors for the Treatment of Inflammatory Acne. J Med Chem. 2018 May 10;61(9):4030-4051.
REF 2 Playing against the odds: scaffold hopping from 3D-fragments
REF 3 Tethering identifies fragment that yields potent inhibitors of human caspase-1. Bioorg Med Chem Lett. 2006 Feb;16(3):559-62.
REF 4 Crystal structure of caspase-1 in complex with VX-765
REF 5 Structural analysis of caspase-1 inhibitors derived from Tethering. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 May 1;61(Pt 5):451-8.
REF 6 Novel Caspase-1 Inhibitors Discovered Using Tethering(SM) with Extenders
REF 7 A common allosteric site and mechanism in caspases. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7595-600.
REF 8 Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex. Chem Pharm Bull (Tokyo). 1999 Jan;47(1):11-21.
REF 9 Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1beta converting enzyme (ICE or caspase 1). Bioorg Med Chem Lett. 2010 Sep 1;20(17):5184-90.
REF 10 Crystal structure of human Caspase-1 with 2-((2-naphthoyl)-L-valyl)-4-hydroxy-N-((3S)-2-hydroxy-5-oxotetrahydrofuran-3-yl)-2-azabicyclo[2.2.2]octane-3-carboxamide (Compound 1)

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