Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T79570 | Target Info | |||
| Target Name | Aggrecanase-1 (ADAMTS4) | ||||
| Synonyms | Aggrecanase 1; ADMP-1; ADAMTS4; ADAM-TS4; ADAM-TS 4; A disintegrin and metalloproteinase with thrombospondin motifs 4 | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | ADAMTS4 | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: N-({4'-[(4-Isobutyrylphenoxy)methyl]biphenyl-4-Yl}sulfonyl)-D-Valine | Ligand Info | |||||
| Structure Description | Crystal structure of ADAMTS4 with inhibitor bound | PDB:2RJP | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [1] |
| PDB Sequence |
ASLSRFVETL
223 VVADDKMAAF233 HGAGLKRYLL243 TVMAAAAKAF253 KHPSIRNPVS263 LVVTRLVILE 277 GPQVGPSAAQ287 TLRSFCAWQR297 GLNTPEDSDP307 DHFDTAILFT317 RQDLCGVSTC 327 DTLGMADVGT337 VCDPARSCAI347 VEDDGLQSAF357 TAAHQLGHVF367 NMLHDNSKPC 377 ISLNGPLSTS387 RHVMAPVMAH397 VDPEEPWSPC407 SARFITDFLD417 NGYGHCLLDK 427 PEAPLHLPVT437 FPGKDYDADR447 QCQLTFGPDS457 RHCPQLPPPC467 AALWCSGHLN 477 GHAMCQTKHS487 PWADGTPCGP497 AQACMGGRCL507 H
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ALA248
3.957
ALA252
3.526
ASP328
4.262
THR329
3.268
LEU330
2.832
GLY331
3.065
MET332
3.641
PHE357
3.135
THR358
3.952
ALA360
4.167
HIS361
3.314
GLN362
3.022
HIS365
3.385
HIS371
2.800
|
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| Ligand Name: 2-(4-Chlorophenoxy)-N-{[(4r)-4-Methyl-2,5-Dioxoimidazolidin-4-Yl]methyl}acetamide | Ligand Info | |||||
| Structure Description | Crystal structure of human ADAMTS-4 in complex with inhibitor (compound 1, 2-(4-chlorophenoxy)-N-{[(4R)-4-methyl-2,5-dioxoimidazolidin-4-yl]methyl} acetamide) | PDB:4WK7 | ||||
| Method | X-ray diffraction | Resolution | 1.24 Å | Mutation | No | [2] |
| PDB Sequence |
SRFVETLVVA
226 DDKMAAFHGA236 GLKRYLLTVM246 AAAAKAFKHP256 SIRNPVSLVV266 TRLVILGPQV 281 GPSAAQTLRS291 FCAWQRGLNT301 PEDSDPDHFD311 TAILFTRQDL321 CGVSTCDTLG 331 MADVGTVCDP341 ARSCAIVEDD351 GLQSAFTAAH361 ELGHVFNMLH371 DNSKPCISLN 381 GPLSRHVMAP393 VMAHVDPEEP403 WSPCSARFIT413 DFLDNGYGHC423 LLDKPEAPL |
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| Ligand Name: 5-Chloro-N-{[(4s)-4-(1-Methyl-1h-Imidazol-2-Yl)-2,5-Dioxoimidazolidin-4-Yl]methyl}-1-Benzofuran-2-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of human ADAMTS-4 in complex with inhibitor 5-CHLORO-N-{[(4S)-4-(1-METHYL-1H-IMIDAZOL-2-YL)-2,5-DIOXOIMIDAZOLIDIN-4-YL]METHYL}-1-BENZOFURAN-2-CARBOXAMIDE (compound 11) | PDB:4WKI | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [2] |
| PDB Sequence |
SLSRFVETLV
224 VADDKMAAFH234 GAGLKRYLLT244 VMAAAAKAFK254 HPSIRNPVSL264 VVTRLVILGP 279 QVGPSAAQTL289 RSFCAWQRGL299 NTPEDSDPDH309 FDTAILFTRQ319 DLCGVSTCDT 329 LGMADVGTVC339 DPARSCAIVE349 DDGLQSAFTA359 AHELGHVFNM369 LHDNSKPCIS 379 LNGPLSRHVM391 APVMAHVDPE401 EPWSPCSARF411 ITDFLDNGYG421 HCLLDKPEAP 431 LHLP
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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 .3PW or .3PW2 or .3PW3 or :33PW;style chemicals stick;color identity;select .A:323 or .A:328 or .A:329 or .A:330 or .A:331 or .A:332 or .A:333 or .A:357 or .A:358 or .A:361 or .A:362 or .A:365 or .A:371 or .A:389 or .A:390 or .A:392 or .A:393 or .A:394 or .A:395 or .A:396 or .A:398; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY323
4.577
ASP328
4.930
THR329
3.016
LEU330
2.838
GLY331
2.957
MET332
3.750
ALA333
4.889
PHE357
4.015
THR358
4.157
HIS361
3.279
GLU362
2.684
|
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| Ligand Name: 5-Chloro-N-{[(4r)-2,5-Dioxo-4-(1,3-Thiazol-2-Yl)imidazolidin-4-Yl]methyl}-1-Benzofuran-2-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of human ADAMTS-4 in complex with inhibitor 5-chloro-N-{[(4R)-2,5-dioxo-4-(1,3-thiazol-2-yl)imidazolidin-4-yl]methyl}-1-benzofuran-2-carboxamide (compound 10) | PDB:4WKE | ||||
| Method | X-ray diffraction | Resolution | 1.62 Å | Mutation | No | [2] |
| PDB Sequence |
LSRFVETLVV
225 ADDKMAAFHG235 AGLKRYLLTV245 MAAAAKAFKH255 PSIRNPVSLV265 VTRLVILEGP 279 QVGPSAAQTL289 RSFCAWQRGL299 NTPEDSDPDH309 FDTAILFTRQ319 DLCGVSTCDT 329 LGMADVGTVC339 DPARSCAIVE349 DDGLQSAFTA359 AHELGHVFNM369 LHDNSKPCIS 379 LNGPLSRHVM391 APVMAHVDPE401 EPWSPCSARF411 ITDFLDNGYG421 HCLLDKPEAP 431 LHLP
|
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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 .3PU or .3PU2 or .3PU3 or :33PU;style chemicals stick;color identity;select .A:323 or .A:329 or .A:330 or .A:331 or .A:332 or .A:333 or .A:357 or .A:358 or .A:361 or .A:362 or .A:365 or .A:371 or .A:389 or .A:390 or .A:391 or .A:392 or .A:393 or .A:394 or .A:395 or .A:396 or .A:398; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY323
4.789
THR329
3.336
LEU330
2.799
GLY331
2.831
MET332
3.678
ALA333
4.900
PHE357
3.920
THR358
4.123
HIS361
3.213
GLU362
2.607
HIS365
3.553
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5. Protein Sci. 2008 Jan;17(1):16-21. | ||||
| REF 2 | Identification of potent and selective hydantoin inhibitors of aggrecanase-1 and aggrecanase-2 that are efficacious in both chemical and surgical models of osteoarthritis. J Med Chem. 2014 Dec 26;57(24):10476-85. | ||||
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