Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T08499 | Target Info | |||
| Target Name | Caterpiller protein 1.1 (NLRP3) | ||||
| Synonyms | PYRIN-containing APAF1-like protein 1; PYPAF1; NALP3; NACHT, LRR and PYD domains-containing protein 3; Cryopyrin; Cold-induced autoinflammatory syndrome 1 protein; CLR1.1; CIAS1; C1orf7; Angiotensin/vasopressin receptor AII/AVP-like | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | NLRP3 | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: MCC950 | Ligand Info | |||||
| Structure Description | Cryo-EM structure of the NLRP3 decamer bound to the inhibitor CRID3 | PDB:7PZC | ||||
| Method | Electron microscopy | Resolution | 3.90 Å | Mutation | No | [1] |
| PDB Sequence |
MASTRCKLAR
12 YLEDLEDVDL22 KKFKMHLEDY32 PPQKGCIPLP42 RGQTEKADHV52 DLATLMIDFN 62 GEEKAWAMAV72 WIFAAINRRD82 LYEKAKRDEP92 KWGSDNARVS102 NPTVICQEDS 112 IEEEWMGLLE122 YLSRISICKM132 KKDYRKKYRK142 YVRSRFQCIE152 ESVSLNKRYT 169 RLRLIKEHRS179 QSPVSPIKME206 LLFDPDDEHS216 EPVHTVVFQG226 AAGIGKTILA 236 RKMMLDWASG246 TLYQDRFDYL256 FYIHCREVSL266 VTQRSLGDLI276 MSCCPDPNPP 286 IHKIVRKPSR296 ILFLMDGFDE306 LQGAFDEHIG316 PLCTDWQKAE326 RGDILLSSLI 336 RKKLLPEASL346 LITTRPVALE356 KLQHLLDHPR366 HVEILGFSEA376 KRKEYFFKYF 386 SDEAQARAAF396 SLIQENEVLF406 TMCFIPLVCW416 IVCTGLKQQM426 ESGKSLAQTS 436 KTTTAVYVFF446 LSSLLQPRGG456 SQEHGLCAHL466 WGLCSLAADG476 IWNQKILFEE 486 SDLRNHGLQK496 ADVSAFLRMN506 LFQKEVDCEK516 FYSFIHMTFQ526 EFFAAMYYLL 536 EEEKEGRTNV546 PGSRLKLPSR556 DVTVLLENYG566 KFEKGYLIFV576 VRFLFGLVNQ 586 ERTSYLEKKL596 SCKISQQIRL606 ELLKWIEVKA616 KAKKLQIQPS626 QLELFYCLYE 636 MQEEDFVQRA646 MDYFPKIEIN656 LSTRMDHMVS666 SFCIENCHRV676 ESLSLGFLHN 686 MPKEEEEEEK696 EGRHLDMVQC706 VLPSSSHAAC716 SHGLVNSHLT726 SSFCRGLFSV 736 LSTSQSLTEL746 DLSDNSLGDP756 GMRVLCETLQ766 HPGCNIRRLW776 LGRCGLSHEC 786 CFDISLVLSS796 NQKLVELDLS806 DNALGDFGIR816 LLCVGLKHLL826 CNLKKLWLVS 836 CCLTSACCQD846 LASVLSTSHS856 LTRLYVGENA866 LGDSGVAILC876 EKAKNPQCNL 886 QKLGLVNSGL896 TSVCCSALSS906 VLSTNQNLTH916 LYLRGNTLGD926 KGIKLLCEGL 936 LHPDCKLQVL946 ELDNCNLTSH956 CCWDLSTLLT966 SSQSLRKLSL976 GNNDLGDLGV 986 MMFCEVLKQQ996 SCLLQNLGLS1006 EMYFNYETKS1016 ALETLQEEKP1026 ELTVVFEPSW 1036
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ALA227
3.352
ALA228
2.616
GLY229
4.980
ARG351
3.460
PRO352
4.196
VAL353
4.671
MET408
3.083
ILE411
3.850
LEU413
4.787
VAL414
3.926
THR439
3.716
|
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| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | Crystal Structure of NLRP3 NACHT domain in complex with a potent inhibitor | PDB:7ALV | ||||
| Method | X-ray diffraction | Resolution | 2.83 Å | Mutation | No | [2] |
| PDB Sequence |
KDYRKKYRKY
143 VRSRFQCIEL164 NKRYTRLRLI174 KEHSPIKMEL207 LFDPDEPVHT221 VVFQGAAGIG 231 KTILARKMML241 DWASGTLYQD251 RFDYLFYIHC261 REVSLVTQRS271 LGDLIMSCCP 281 DPNPPIHKIV291 RKPSRILFLM301 DGFDELQGAF311 DEHIGPLCTD321 WQKAERGDIL 331 LSSLIRKKLL341 PEASLLITTR351 PVALEKLQHL361 LDHPRHVEIL371 GFSEAKRKEY 381 FFKYFSDEAQ391 ARAAFSLIQE401 NEVLFTMCFI411 PLVCWIVCTG421 LKQQMESGKS 431 LAQTSKTTTA441 VYVFFLSSLL451 CAHLWGLCSL472 AADGIWNQKI482 LFEESDLRNH 492 GLQDVSAFLR504 MNLFQKEVKF517 YSFIHMTFQE527 FFAAMYYLLE537 ESRDVTVLLE 563 NYGKFEKGYL573 IFVVRFLFGL583 VNQERSYLEK594 KLSCKISQQI604 RLELLKWIEV 614 KAKAKKLQIQ624 PSQLELFYCL634 YEMQEEDFVQ644 RAMDYFPKIE654 INLSTRMDHM 664 VSSFCIENCH674 RV
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ARG167
3.366
TYR168
3.342
THR169
2.765
ARG170
4.973
LEU171
3.556
GLY226
4.909
ALA227
3.728
ALA228
3.969
GLY229
3.040
ILE230
3.761
GLY231
3.114
|
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 1-[4-(2-Hydroxypropan-2-yl)furan-2-yl]sulfonyl-3-(1,2,3,5-tetrahydro-s-indacen-4-yl)urea | Ligand Info | |||||
| Structure Description | Cryo-EM structure of PYD-deleted human NLRP3 hexamer | PDB:7VTP | ||||
| Method | Electron microscopy | Resolution | 3.23 Å | Mutation | No | [3] |
| PDB Sequence |
DYRKKYRKYV
144 RSRFQCISVS163 LNKRYTRLRL173 IKEHRSPIKM205 ELLFDPDDEH215 SEPVHTVVFQ 225 GAAGIGKTIL235 ARKMMLDWAS245 GTLYQDRFDY255 LFYIHCREVS265 LVTQRSLGDL 275 IMSCCPDPNP285 PIHKIVRKPS295 RILFLMDGFD305 ELQGAFDEHI315 GPLCTDWQKA 325 ERGDILLSSL335 IRKKLLPEAS345 LLITTRPVAL355 EKLQHLLDHP365 RHVEILGFSE 375 AKRKEYFFKY385 FSDEAQARAA395 FSLIQENEVL405 FTMCFIPLVC415 WIVCTGLKQQ 425 MESGKSLAQT435 SKTTTAVYVF445 FLSSLLLCAH465 LWGLCSLAAD475 GIWNQKILFE 485 ESDLRNHGLQ495 KADVSAFLRM505 NLFKFYSFIH522 MTFQEFFAAM532 YYLLPSRDVT 559 VLLENYGKFE569 KGYLIFVVRF579 LFGLVNQERT589 SYLEKKLSCK599 ISQQIRLELL 609 KWIEVKAKAK619 KLQIQPSQLE629 LFYCLYEMQE639 EDFVQRAMDY649 FPKIEINLST 659 RMDHMVSSFC669 IENCHRVESL679 SLGFLHTSSF729 CRGLFSVLST739 SQSLTELDLS 749 DNSLGDPGMR759 VLCETLQHPG769 CNIRRLWLGR779 CGLSHECCFD789 ISLVLSSNQK 799 LVELDLSDNA809 LGDFGIRLLC819 VGLKHLLCNL829 KKLWLVSCCL839 TSACCQDLAS 849 VLSTSHSLTR859 LYVGENALGD869 SGVAILCEKA879 KNPQCNLQKL889 GLVNSGLTSV 899 CCSALSSVLS909 TNQNLTHLYL919 RGNTLGDKGI929 KLLCEGLLHP939 DCKLQVLELD 949 NCNLTSHCCW959 DLSTLLTSSQ969 SLRKLSLGNN979 DLGDLGVMMF989 CEVLKQQSCL 999 LQNLGLSEMY1009 FNYETKSALE1019 TLQEEKPELT1029 VVFEP
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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 .7YN or .7YN2 or .7YN3 or :37YN;style chemicals stick;color identity;select .A:226 or .A:227 or .A:228 or .A:351 or .A:352 or .A:408 or .A:410 or .A:411 or .A:413 or .A:414 or .A:439 or .A:443 or .A:524 or .A:575 or .A:578 or .A:628 or .A:629 or .A:632 or .A:661 or .A:662; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY226
4.393
ALA227
3.330
ALA228
3.065
ARG351
3.327
PRO352
3.692
MET408
4.615
PHE410
4.099
ILE411
3.345
LEU413
4.339
VAL414
3.979
|
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| Ligand Name: Nlrp3-IN-5 | Ligand Info | |||||
| Structure Description | Crystal Structure of NLRP3 NACHT domain in complex with a potent inhibitor | PDB:7ALV | ||||
| Method | X-ray diffraction | Resolution | 2.83 Å | Mutation | No | [2] |
| PDB Sequence |
KDYRKKYRKY
143 VRSRFQCIEL164 NKRYTRLRLI174 KEHSPIKMEL207 LFDPDEPVHT221 VVFQGAAGIG 231 KTILARKMML241 DWASGTLYQD251 RFDYLFYIHC261 REVSLVTQRS271 LGDLIMSCCP 281 DPNPPIHKIV291 RKPSRILFLM301 DGFDELQGAF311 DEHIGPLCTD321 WQKAERGDIL 331 LSSLIRKKLL341 PEASLLITTR351 PVALEKLQHL361 LDHPRHVEIL371 GFSEAKRKEY 381 FFKYFSDEAQ391 ARAAFSLIQE401 NEVLFTMCFI411 PLVCWIVCTG421 LKQQMESGKS 431 LAQTSKTTTA441 VYVFFLSSLL451 CAHLWGLCSL472 AADGIWNQKI482 LFEESDLRNH 492 GLQDVSAFLR504 MNLFQKEVKF517 YSFIHMTFQE527 FFAAMYYLLE537 ESRDVTVLLE 563 NYGKFEKGYL573 IFVVRFLFGL583 VNQERSYLEK594 KLSCKISQQI604 RLELLKWIEV 614 KAKAKKLQIQ624 PSQLELFYCL634 YEMQEEDFVQ644 RAMDYFPKIE654 INLSTRMDHM 664 VSSFCIENCH674 RV
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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 .RM5 or .RM52 or .RM53 or :3RM5;style chemicals stick;color identity;select .A:226 or .A:227 or .A:228 or .A:229 or .A:351 or .A:352 or .A:353 or .A:408 or .A:410 or .A:411 or .A:413 or .A:414 or .A:439 or .A:443 or .A:524 or .A:574 or .A:575 or .A:578 or .A:579 or .A:624 or .A:626 or .A:628 or .A:629 or .A:632 or .A:661 or .A:662; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY226
4.595
ALA227
3.359
ALA228
2.981
GLY229
4.746
ARG351
2.818
PRO352
3.438
VAL353
4.160
MET408
3.549
PHE410
3.543
ILE411
3.483
LEU413
4.544
VAL414
4.684
THR439
3.094
|
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| Ligand Name: (6S,8R)-N-[(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl]-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonamide | Ligand Info | |||||
| Structure Description | CryoEM Structure of NLRP3 NACHT domain in complex with G2394 | PDB:8ETR | ||||
| Method | Electron microscopy | Resolution | 3.50 Å | Mutation | No | [4] |
| PDB Sequence |
KDYRKKYRKY
143 VRSRFQCILN165 KRYTRLRLIK175 EHIKMELLFD210 PDEPVHTVVF224 QGAAGIGKTI 234 LARKMMLDWA244 SGTLYQDRFD254 YLFYIHCREV264 SLVTQRSLGD274 LIMSCCPDPN 284 PPIHKIVRKP294 SRILFLMDGF304 DELQGAFDEH314 IGPLCTDWQK324 AERGDILLSS 334 LIRKKLLPEA344 SLLITTRPVA354 LEKLQHLLDH364 PRHVEILGFS374 EAKRKEYFFK 384 YFSDEAQARA394 AFSLIQENEV404 LFTMCFIPLV414 CWIVCTGLKQ424 QMESGKSLAQ 434 TSKTTTAVYV444 FFLSSLLCAH465 LWGLCSLAAD475 GIWNQKILFE485 ESDLRNHGLQ 495 KADVSAFLRM505 NLFQKEVKFY518 SFIHMTFQEF528 FAAMYYLLEE538 SRDVTVLLEN 564 YGKFEKGYLI574 FVVRFLFGLV584 NQERSYLEKK595 LSCKISQQIR605 LELLKWIEVK 615 AKAKKLQIQP625 SQLELFYCLY635 EMQEEDFVQR645 AMDYFPKIEI655 NLSTRMDHMV 665 SSFCIENCHR675 V
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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 .WTN or .WTN2 or .WTN3 or :3WTN;style chemicals stick;color identity;select .A:226 or .A:227 or .A:228 or .A:229 or .A:351 or .A:352 or .A:353 or .A:408 or .A:410 or .A:411 or .A:413 or .A:414 or .A:439 or .A:443 or .A:524 or .A:574 or .A:575 or .A:578 or .A:579 or .A:626 or .A:628 or .A:629 or .A:632 or .A:661 or .A:662; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLY226
4.387
ALA227
2.554
ALA228
2.452
GLY229
4.244
ARG351
2.456
PRO352
3.438
VAL353
4.074
MET408
3.287
PHE410
3.622
ILE411
2.810
LEU413
2.908
VAL414
3.256
THR439
2.847
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3. Nature. 2022 Apr;604(7904):184-189. | ||||
| REF 2 | Crystal Structure of NLRP3 NACHT Domain With an Inhibitor Defines Mechanism of Inflammasome Inhibition. J Mol Biol. 2021 Dec 3;433(24):167309. | ||||
| REF 3 | Structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation. Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2121353119. | ||||
| REF 4 | Overcoming Preclinical Safety Obstacles to Discover (S)-N-((1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonamide (GDC-2394): A Potent and Selective NLRP3 Inhibitor. J Med Chem. 2022 Nov 10;65(21):14721-14739. | ||||
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