Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T13057 | Target Info | |||
| Target Name | Protein-tyrosine phosphatase SHP-2 (PTPN11) | ||||
| Synonyms | Tyrosine-protein phosphatase non-receptor type 11; SHPTP2; SHP2; SHP-2; SH-PTP3; SH-PTP2; Protein-tyrosine phosphatase SHP2; Protein-tyrosine phosphatase 2C; Protein-tyrosine phosphatase 1D; PTP2C; PTP-2C; PTP-1D | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | PTPN11 | ||||
| Biochemical Class | Phosphoric monoester hydrolase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Dodecane-Trimethylamine | Ligand Info | |||||
| Structure Description | TYROSINE PHOSPHATASE SHP-2 | PDB:2SHP | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [1] |
| PDB Sequence |
KSRRWFHPNI
11 TGVEAENLLL21 TRGVDGSFLA31 RPSKSNPGDL41 TLSVRRNGAV51 THIKIQNTGD 61 YYDLYGGEKF71 ATLAELVQYY81 MEHHGQLKEK91 NGDVIELKYP101 LNCADPTSER 111 WFHGHLSGKE121 AEKLLTEKGK131 HGSFLVRESQ141 SHPGDFVLSV151 RTGDNDGKSK 166 VTHVMIRCQE176 LKYDVGGGER186 FDSLTDLVEH196 YKKNPMVETL206 GTVLQLKQPL 216 NTTRINAAEI226 ESRVRELSKG246 FWEEFETLQQ256 QECKLLYSRK266 EGQRQENKNK 276 NRYKNILPFD286 HTRVVLHDSD303 YINANIIMPK324 KSYIATQGCL334 QNTVNDFWRM 344 VFQENSRVIV354 MTTKEVERGK364 SKCVKYWPDE374 YALKEYGVMR384 VRNVKESAAH 394 DYTLRELKLS404 KVGQGNTERT414 VWQYHFRTWP424 DHGVPSDPGG434 VLDFLEEVHH 444 KQESIMDAGP454 VVVHCSAGIG464 RTGTFIVIDI474 LIDIIREKGV484 DCDIDVPKTI 494 QMVRSQRSGM504 VQTEAQYRSI514 YMAVQHYIET524 L
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| Ligand Name: 4-(3-phenylphenyl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3-thiazol-2-amine | Ligand Info | |||||
| Structure Description | The atomic structure of SHP2 E76A mutant in complex with allosteric inhibitor 9b | PDB:5XZR | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
MTSRRWFHPN
10 ITGVEAENLL20 LTRGVDGSFL30 ARPSKSNPGD40 FTLSVRRNGA50 VTHIKIQNTG 60 DYYDLYGGEK70 FATLAALVQY80 YMEHHGQLKE90 KNGDVIELKY100 PLNCADPTSE 110 RWFHGHLSGK120 EAEKLLTEKG130 KHGSFLVRES140 QSHPGDFVLS150 VRTGDDKGES 160 NDGKSKVTHV170 MIRCQELKYD180 VGGGERFDSL190 TDLVEHYKKN200 PMVETLGTVL 210 QLKQPLNTTR220 INAAEIESRV230 RELSKLAEKV243 KQGFWEEFET253 LQQQECKLLY 263 SRKEGQRQEN273 KNKNRYKNIL283 PFDHTRVVLH293 DGDPNEPVSD303 YINANIIMPK 325 SYIATQGCLQ335 NTVNDFWRMV345 FQENSRVIVM355 TTKEVERGKS365 KCVKYWPDEY 375 ALKEYGVMRV385 RNVKESAAHD395 YTLRELKLSK405 VGQGNTERTV415 WQYHFRTWPD 425 HGVPSDPGGV435 LDFLEEVHHK445 QESIMDAGPV455 VVHCSAGIGR465 TGTFIVIDIL 475 IDIIREKGVD485 CDIDVPKTIQ495 MVRSQRSGMV505 QTEAQYRFIY515 MAVQHYIETL 525 QRRIEEEQK
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| Ligand Name: 1-[3-(2,3-dichlorophenyl)-1H-pyrazolo[3,4-b]pyrazin-6-yl]-4-methylpiperidin-4-amine | Ligand Info | |||||
| Structure Description | Structure of human SHP2 in complex with inhibitor IACS-13909 | PDB:6WU8 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [3] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHHGQLKEKN92 GDVIELKYPL102 NCADPTSERW 112 FHGHLSGKEA122 EKLLTEKGKH132 GSFLVRESQS142 HPGDFVLSVR152 TGDDNDGKSK 166 VTHVMIRCQE176 LKYDVGGGER186 FDSLTDLVEH196 YKKNPMVETL206 GTVLQLKQPL 216 NTTRINAAEI226 ESRVRELSKQ245 GFWEEFETLQ255 QQECKLLYSR265 KEGQRQENKN 275 KNRYKNILPF285 DHTRVVLHSD303 YINANIIMPK324 KSYIATQGCL334 QNTVNDFWRM 344 VFQENSRVIV354 MTTKEVERGK364 SKCVKYWPDE374 YALKEYGVMR384 VRNVKESAAH 394 DYTLRELKLS404 KVGQGNTERT414 VWQYHFRTWP424 DHGVPSDPGG434 VLDFLEEVHH 444 KQESIMDAGP454 VVVHCSAGIG464 RTGTFIVIDI474 LIDIIREKGV484 DCDIDVPKTI 494 QMVRSQRSGM504 VQTEAQYRFI514 YMAVQHYIET524 LQRR
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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 .U9Y or .U9Y2 or .U9Y3 or :3U9Y;style chemicals stick;color identity;select .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:113 or .A:114 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4-[6-(4-amino-4-methylpiperidin-1-yl)-1H-pyrazolo[3,4-b]pyrazin-3-yl]-3-chloro-N-methylpyridin-2-amine | Ligand Info | |||||
| Structure Description | Structure of human SHP2 in complex with compound 22 | PDB:7R7D | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [4] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHHGQLKEDV95 IELKYPLNCA105 DPTSERWFHG 115 HLSGKEAEKL125 LTEKGKHGSF135 LVRESQSHPG145 DFVLSVRTGD155 DGKSKVTHVM 171 IRCQELKYDV181 GGGERFDSLT191 DLVEHYKKNP201 MVETLGTVLQ211 LKQPLNTTRI 221 NAAEIESRVR231 ELSKLQGFWE249 EFETLQQQEC259 KLLYSRKEGQ269 RQENKNKNRY 279 KNILPFDHTR289 VVLHDVSDYI305 NANIIMPKKS326 YIATQGCLQN336 TVNDFWRMVF 346 QENSRVIVMT356 TKEVERGKSK366 CVKYWPDEYA376 LKEYGVMRVR386 NVKESAAHDY 396 TLRELKLSKV406 GQGNTERTVW416 QYHFRTWPDH426 GVPSDPGGVL436 DFLEEVHHKQ 446 ESIMDAGPVV456 VHCSAGIGRT466 GTFIVIDILI476 DIIREKGVDC486 DIDVPKTIQM 496 VRSQRSGMVQ506 TEAQYRFIYM516 AVQHYIETL
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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 .37I or .37I2 or .37I3 or :337I;style chemicals stick;color identity;select .A:108 or .A:110 or .A:111 or .A:112 or .A:113 or .A:114 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 6-(4-amino-4-methylpiperidin-1-yl)-3-(3-chlorophenyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one | Ligand Info | |||||
| Structure Description | Structure of human SHP2 in complex with compound 16 | PDB:7R75 | ||||
| Method | X-ray diffraction | Resolution | 2.83 Å | Mutation | No | [4] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EGQLKEKNGD94 VIELKYPLNC104 ADPTSERWFH 114 GHLSGKEAEK124 LLTEKGKHGS134 FLVRESQSHP144 GDFVLSVRTG154 DDNDGKSKVT 168 HVMIRCQELK178 YDVGGGERFD188 SLTDLVEHYK198 KNPMVETLGT208 VLQLKQPLNT 218 TRINAAEIES228 RVRELSKLQG246 FWEEFETLQQ256 QECKLLYSRK266 EGQRQENKNK 276 NRYKNILPFD286 HTRVVLHDGS302 DYINANIIMP312 KKSYIATQGC333 LQNTVNDFWR 343 MVFQENSRVI353 VMTTKEVERG363 KSKCVKYWPD373 EYALKEYGVM383 RVRNVKESAA 393 HDYTLRELKL403 SKVGQGNTER413 TVWQYHFRTW423 PDHGVPSDPG433 GVLDFLEEVH 443 HKQESIMDAG453 PVVVHCSAGI463 GRTGTFIVID473 ILIDIIREKG483 VDCDIDVPKT 493 IQMVRSQRSG503 MVQTEAQYRF513 IYMAVQHYIE523 TLQR
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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 .33I or .33I2 or .33I3 or :333I;style chemicals stick;color identity;select .A:108 or .A:110 or .A:111 or .A:113 or .A:114 or .A:216 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:251 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495 or .A:511; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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THR108
3.461
GLU110
3.787
ARG111
3.059
PHE113
2.428
HIS114
3.830
LEU216
4.841
ASN217
3.839
THR218
3.696
THR219
3.763
GLU249
3.674
|
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| Ligand Name: [3-(4-Amino-4-methylpiperidin-1-yl)-6-(2,3-dichlorophenyl)-5-methylpyrazin-2-yl]methanol | Ligand Info | |||||
| Structure Description | Structure of human SHP2 in complex with compound 27 | PDB:7R7I | ||||
| Method | X-ray diffraction | Resolution | 2.85 Å | Mutation | No | [4] |
| PDB Sequence |
RRWFHPNITG
13 VEAENLLLTR23 GVDGSFLARP33 SKSNPGDFTL43 SVRRNGAVTH53 IKIQNTGDYY 63 DLYGGEKFAT73 LAELVQYYME83 HHGQLKEKNG93 DVIELKYPLN103 CADPTSERWF 113 HGHLSGKEAE123 KLLTEKGKHG133 SFLVRESQSH143 PGDFVLSVRT153 GGKSKVTHVM 171 IRCQELKYDV181 GGGERFDSLT191 DLVEHYKKNP201 MVETLGTVLQ211 LKQPLNTTRI 221 NAAEIESRVR231 ELSKLQGFWE249 EFETLQQQEC259 KLLYSRKEGQ269 RQENKNKNRY 279 KNILPFDHTR289 VVLHDGSDYI305 NANIIMPKKS326 YIATQGCLQN336 TVNDFWRMVF 346 QENSRVIVMT356 TKEVERGKSK366 CVKYWPDEYA376 LKEYGVMRVR386 NVKESAAHDY 396 TLRELKLSKV406 GQGNTERTVW416 QYHFRTWPDH426 GVPSDPGGVL436 DFLEEVHHKQ 446 ESIMDAGPVV456 VHCSAGIGRT466 GTFIVIDILI476 DIIREKGVDC486 DIDVPKTIQM 496 VRSQRSGMVQ506 TEAQYRFIYM516 AVQHYIETL
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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 .3CW or .3CW2 or .3CW3 or :33CW;style chemicals stick;color identity;select .A:108 or .A:110 or .A:111 or .A:113 or .A:114 or .A:216 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 6-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-(2,3-dichlorophenyl)-2-methylpyrimidin-4(3H)-one | Ligand Info | |||||
| Structure Description | Structure of human SHP2 in complex with compound 30 | PDB:7R7L | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [4] |
| PDB Sequence |
TSRRWFHPNI
11 TGVEAENLLL21 TRGVDGSFLA31 RPSKSNPGDF41 TLSVRRNGAV51 THIKIQNTGD 61 YYDLYGGEKF71 ATLAELVQYY81 MEHHGQLVIE97 LKYPLNCADP107 TSERWFHGHL 117 SGKEAEKLLT127 EKGKHGSFLV137 RESQSHPGDF147 VLSVRTGDSK166 VTHVMIRCQE 176 LKYDVGGGER186 FDSLTDLVEH196 YKKNPMVETL206 GTVLQLKQPL216 NTTRINAAEI 226 ESRVRELSKG246 FWEEFETLQQ256 QECKLLYSRK266 EGQRQENKNK276 NRYKNILPFD 286 HTRVVLHDGD296 PNEPVSDYIN306 ANIIMPEFKK325 SYIATQGCLQ335 NTVNDFWRMV 345 FQENSRVIVM355 TTKEVERGKS365 KCVKYWPDEY375 ALKEYGVMRV385 RNVKESAAHD 395 YTLRELKLSK405 VGQGNTERTV415 WQYHFRTWPD425 HGVPSDPGGV435 LDFLEEVHHK 445 QESIMDAGPV455 VVHCSAGIGR465 TGTFIVIDIL475 IDIIREKGVD485 CDIDVPKTIQ 495 MVRSQRSGMV505 QTEAQYRFIY515 MAVQHYIETL525
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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 .3ED or .3ED2 or .3ED3 or :33ED;style chemicals stick;color identity;select .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:112 or .A:113 or .A:114 or .A:115 or .A:216 or .A:218 or .A:219 or .A:249 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495 or .A:511; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO107
4.435
THR108
2.689
SER109
4.749
GLU110
3.003
ARG111
3.586
TRP112
4.945
PHE113
2.497
HIS114
3.354
GLY115
4.896
LEU216
4.976
THR218
3.837
|
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| Ligand Name: 6-(4-Azanyl-4-Methyl-Piperidin-1-Yl)-3-[2,3-Bis(Chloranyl)phenyl]pyrazin-2-Amine | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor SHP099 | PDB:5EHR | ||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [5] |
| PDB Sequence |
RRWFHPNITG
13 VEAENLLLTR23 GVDGSFLARP33 SKSNPGDFTL43 SVRRNGAVTH53 IKIQNTGDYY 63 DLYGGEKFAT73 LAELVQYYME83 HIELKYPLNC104 ADPTSERWFH114 GHLSGKEAEK 124 LLTEKGKHGS134 FLVRESGDFV148 LSVRTGDSKV167 THVMIRCQEL177 KYDVGGGERF 187 DSLTDLVEHY197 KKNPMVETLG207 TVLQLKQPLN217 TTRINAAEIE227 SRVRELSKLA 237 KQGFWEEFET253 LQQQECKLLY263 SRKEGQRQEN273 KNKNRYKNIL283 PFDHTRVVLH 293 DGDPNEPVSD303 YINANIIMPE313 FKPKKSYIAT330 QGCLQNTVND340 FWRMVFQENS 350 RVIVMTTKEV360 ERGKSKCVKY370 WPDEYALKEY380 GVMRVRNVKE390 SAAHDYTLRE 400 LKLSKVGQGN410 TERTVWQYHF420 RTWPDHGVPS430 DPGGVLDFLE440 EVHHKQESIM 450 DAGPVVVHCS460 AGIGRTGTFI470 VIDILIDIIR480 EKGVDCDIDV490 PKTIQMVRSQ 500 RSGMVQTEAQ510 YRFIYMAVQH520 YIETL
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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 .5OD or .5OD2 or .5OD3 or :35OD;style chemicals stick;color identity;select .A:108 or .A:110 or .A:111 or .A:112 or .A:113 or .A:114 or .A:218 or .A:219 or .A:249 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495 or .A:511; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 5-[2,3-Bis(Chloranyl)phenyl]-2-[(3~{r},5~{s})-3,5-Dimethylpiperazin-1-Yl]pyrimidin-4-Amine | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor SHP836 | PDB:5EHP | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [6] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHQLKEKNGD94 VIELKYPLNC104 ADPTSERWFH 114 GHLSGEAEKL125 LTEKGKHGSF135 LVRESSHPGD146 FVLSVRTGSK166 VTHVMIRCQE 176 LKYDVGGGER186 FDSLTDLVEH196 YKKNPMVELG207 TVLQLKQPLN217 TTRINAAEIE 227 SRVRELSKLA237 KQGFWEEFET253 LQQQECKLLY263 SRKEGQRQEN273 KNKNRYKNIL 283 PFDHTRVVLH293 DGPNEPVSDY304 INANIIMPEF314 KPKKSYIATQ331 GCLQNTVNDF 341 WRMVFQENSR351 VIVMTTKEVE361 RGKSKCVKYW371 PDEYALKEYG381 VMRVRNVKES 391 AAHDYTLREL401 KLSKVGQGNT411 ERTVWQYHFR421 TWPDHGVPSD431 PGGVLDFLEE 441 VHHKQESIMD451 AGPVVVHCSA461 GIGRTGTFIV471 IDILIDIIRE481 KGVDCDIDVP 491 KTIQMVRSQR501 SGMVQTEAQY511 RFIYMAVQHY521 IETL
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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 .5OA or .5OA2 or .5OA3 or :35OA;style chemicals stick;color identity;select .A:108 or .A:110 or .A:111 or .A:113 or .A:114 or .A:218 or .A:219 or .A:249 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495 or .A:511; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 2-[4-(aminomethyl)-4-methylpiperidin-1-yl]-5-{[2-(trifluoromethyl)pyridin-3-yl]sulfanyl}pyrimidin-4(3H)-one | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Pyrimidinone 7 | PDB:6MD7 | ||||
| Method | X-ray diffraction | Resolution | 1.96 Å | Mutation | No | [7] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHHGQLKENG93 DVIELKYPLN103 CADPTSERWF 113 HGHLSGKEAE123 KLLTEKGKHG133 SFLVRESQSH143 PGDFVLSVRT153 GDNDGKSKVT 168 HVMIRCQELK178 YDVGGGERFD188 SLTDLVEHYK198 KNPMVETLGT208 VLQLKQPLNT 218 TRINAAEIES228 RVRELSKLQG246 FWEEFETLQQ256 QECKLLYSRK266 EGQRQENKNK 276 NRYKNILPFD286 HTRVVLHDGD296 PPVSDYINAN308 IIMPEKSYIA329 TQGCLQNTVN 339 DFWRMVFQEN349 SRVIVMTTKE359 VERGKSKCVK369 YWPDEYALKE379 YGVMRVRNVK 389 ESAAHDYTLR399 ELKLSKVGQG409 NTERTVWQYH419 FRTWPDHGVP429 SDPGGVLDFL 439 EEVHHKQESI449 MDAGPVVVHC459 SAGIGRTGTF469 IVIDILIDII479 REKGVDCDID 489 VPKTIQMVRS499 QRSGMVQTEA509 QYRFIYMAVQ519 HYIETL
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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 .JE1 or .JE12 or .JE13 or :3JE1;style chemicals stick;color identity;select .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:113 or .A:114 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 3-[4-[(2-Chlorophenyl)methyl]-5-oxo-[1,2,4]triazolo[4,3-a]quinazolin-1-yl]-4-hydroxybenzoic acid | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor SHP504 | PDB:6BMV | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [8] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHHGQLKNGD94 VIELKYPLNC104 ADPTSERWFH 114 GHLSGKEAEK124 LLTEKGKHGS134 FLVRESQPGD146 FVLSVRTGSK166 VTHVMIRCQE 176 LKYDVGGGER186 FDSLTDLVEH196 YKKNPMVETL206 GTVLQLKQPL216 NTTRINAAEI 226 ESRVRELSKQ245 GFWEEFETLQ255 QQECKLLYSR265 KEGQRQENKN275 KNRYKNILPF 285 DHTRVVLHPV301 SDYINANIIM311 PEKSYIATQG332 CLQNTVNDFW342 RMVFQENSRV 352 IVMTTKEVER362 GKSKCVKYWP372 DEYALKEYGV382 MRVRNVKESA392 AHDYTLRELK 402 LSKVGQGNTE412 RTVWQYHFRT422 WPDHGVPSDP432 GGVLDFLEEV442 HHKQESIMDA 452 GPVVVHCSAG462 IGRTGTFIVI472 DILIDIIREK482 GVDCDIDVPK492 TIQMVRSQRS 502 GMVQTEAQYR512 FIYMAVQHYI522 ETL
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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 .DZS or .DZS2 or .DZS3 or :3DZS;style chemicals stick;color identity;select .A:79 or .A:80 or .A:83 or .A:84 or .A:262 or .A:263 or .A:264 or .A:265 or .A:266 or .A:269 or .A:280 or .A:281 or .A:282 or .A:283; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 5-[(2,3-dichlorophenyl)sulfanyl]-3H-imidazo[4,5-b]pyridin-2-amine | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Imidazo-pyridine 24 | PDB:6MDD | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [9] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHGDVIELKY100 PLNCADPTSE110 RWFHGHLSGK 120 EAEKLLTEKG130 KHGSFLVRES140 QSHPGDFVLS150 VRTGDSKVTH169 VMIRCQELKY 179 DVGGGERFDS189 LTDLVEHYKK199 NPMVETLGTV209 LQLKQPLNTT219 RINAAEIESR 229 VRELSKGFWE249 EFETLQQQEC259 KLLYSRKEGQ269 RQENKNKNRY279 KNILPFDHTR 289 VVLHDSDYIN306 ANIIMPKSYI328 ATQGCLQNTV338 NDFWRMVFQE348 NSRVIVMTTK 358 EVERGKSKCV368 KYWPDEYALK378 EYGVMRVRNV388 KESAAHDYTL398 RELKLSKVGQ 408 GNTERTVWQY418 HFRTWPDHGV428 PSDPGGVLDF438 LEEVHHKQES448 IMDAGPVVVH 458 CSAGIGRTGT468 FIVIDILIDI478 IREKGVDCDI488 DVPKTIQMVR498 SQRSGMVQTE 508 AQYRFIYMAV518 QHYIETL
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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 .JE7 or .JE72 or .JE73 or :3JE7;style chemicals stick;color identity;select .A:111 or .A:113 or .A:114 or .A:216 or .A:217 or .A:218 or .A:219 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Ligand Name: 1-(3-chloro-4-{[1-(2-hydroxy-3-methoxyphenyl)-5-oxo[1,2,4]triazolo[4,3-a]quinazolin-4(5H)-yl]methyl}benzene-1-carbonyl)-L-proline | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitors SHP099 and SHP844 | PDB:6BMY | ||||
| Method | X-ray diffraction | Resolution | 2.09 Å | Mutation | No | [8] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSNPGDFTLS44 VRRNGAVTHI54 KIQNTGDYYD 64 LYGGEKFATL74 AELVQYYMEH84 HGQLKGDVIE97 LKYPLNCADP107 TSERWFHGHL 117 EKLLTEKGKH132 GSFLVRESPG145 DFVLSVRTGS165 KVTHVMIRCQ175 ELKYDVGGGE 185 RFDSLTDLVE195 HYKKNPMVET205 LGTVLQLKQP215 LNTTRINAAE225 IESRVRELSK 235 LQGFWEEFET253 LQQQECKLLY263 SRKEGQRQEN273 KNKNRYKNIL283 PFDHTRVVLH 293 DGDPPVSDYI305 NANIIMPPKK325 SYIATQGCLQ335 NTVNDFWRMV345 FQENSRVIVM 355 TTKEVERGKS365 KCVKYWPDEY375 ALKEYGVMRV385 RNVKESAAHD395 YTLRELKLSK 405 VGQGNTERTV415 WQYHFRTWPD425 HGVPSDPGGV435 LDFLEEVHHK445 QESIMDAGPV 455 VVHCSAGIGR465 TGTFIVIDIL475 IDIIREKGVD485 CDIDVPKTIQ495 MVRSQRSGMV 505 QTEAQYRFIY515 MAVQHYIETL525
|
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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 .DYV or .DYV2 or .DYV3 or :3DYV;style chemicals stick;color identity;select .A:71 or .A:79 or .A:80 or .A:83 or .A:84 or .A:87 or .A:262 or .A:263 or .A:264 or .A:265 or .A:266 or .A:269 or .A:274 or .A:280 or .A:281 or .A:283; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Shp2-IN-8 | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor TK-453 | PDB:7VXG | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [10] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHIELKYPLN103 CADPTSERWF113 HLSGKEAEKL 125 LTEKGKHGSF135 LVRESQSHPG145 DFVLSVRTGD155 SKVTHVMIRC174 QELKYDVGGG 184 ERFDSLTDLV194 EHYKKNPMVE204 TLGTVLQLKQ214 PLNTTRINAA224 EIESRVRELS 234 KGFWEEFETL254 QQQECKLLYS264 RKEGQRQENK274 NKNRYKNILP284 FDHTRVVLHD 294 GDPEPVSDYI305 NANIIMPKSY327 IATQGCLQNT337 VNDFWRMVFQ347 ENSRVIVMTT 357 KEVERGKSKC367 VKYWPDEYAL377 KEYGVMRVRN387 VKESAAHDYT397 LRELKLSKVG 407 QGNTERTVWQ417 YHFRTWPDHG427 VPSDPGGVLD437 FLEEVHHKQE447 SIMDAGPVVV 457 HCSAGIGRTG467 TFIVIDILID477 IIRKGVDCDI488 DVPKTIQMVR498 SQRSGMVQTE 508 AQYRFIYMAV518 QHYIETL
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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 .83Q or .83Q2 or .83Q3 or :383Q;style chemicals stick;color identity;select .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:112 or .A:113 or .A:114 or .A:215 or .A:216 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:251 or .A:252 or .A:253 or .A:254 or .A:255 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495 or .A:511; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO107
3.766
THR108
1.649
SER109
2.586
GLU110
2.614
ARG111
2.218
TRP112
4.379
PHE113
2.333
HIS114
2.692
PRO215
4.943
LEU216
4.761
ASN217
2.825
THR218
2.701
THR219
2.380
|
|||||
| Ligand Name: 3-(2-chlorophenyl)-6-{4-[(dimethylamino)methyl]phenyl}-5-methyl[1,2]oxazolo[4,5-c]pyridin-4(5H)-one | Ligand Info | |||||
| Structure Description | NON-RECEPTOR PROTEIN TYROSINE PHOSPHATASE SHP2 IN COMPLEX WITH ALLOSTERIC INHIBITOR Isoxazolo-pyridinone 3 | PDB:6MD9 | ||||
| Method | X-ray diffraction | Resolution | 2.12 Å | Mutation | No | [9] |
| PDB Sequence |
RRWFHPNITG
13 VEAENLLLTR23 GVDGSFLARP33 SNPGDFTLSV45 RRNGAVTHIK55 IQNTGDYYDL 65 YGGEKFATLA75 ELVQYYMEHI96 ELKYPLNCAD106 PTSERWFHGH116 LSGKEAEKLL 126 TEKGKHGSFL136 VREPGDFVLS150 VRTGDSKVTH169 VMIRCQELKY179 DVGGGERFDS 189 LTDLVEHYKK199 NPMVETLGTV209 LQLKQPLNTT219 RINAAEIESR229 VRELSKLQGF 247 WEEFETLQQQ257 ECKLLYSRKE267 GQRQENKNKN277 RYKNILPFDH287 TRVVLHSDYI 305 NANIIMPKSY327 IATQGCLQNT337 VNDFWRMVFQ347 ENSRVIVMTT357 KEVERGKSKC 367 VKYWPDEYAL377 KEYGVMRVRN387 VKESAAHDYT397 LRELKLSKVG407 QGNTERTVWQ 417 YHFRTWPDHG427 VPSDPGGVLD437 FLEEVHHKQE447 SIMDAGPVVV457 HCSAGIGRTG 467 TFIVIDILID477 IIREKGVDCD487 IDVPKTIQMV497 RSQRSGMVQT507 EAQYRFIYMA 517 VQHYIETL
|
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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 .JEJ or .JEJ2 or .JEJ3 or :3JEJ;style chemicals stick;color identity;select .A:110 or .A:111 or .A:113 or .A:114 or .A:115 or .A:216 or .A:217 or .A:218 or .A:219 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 4-(2-Chlorobenzyl)-1-(2-hydroxy-3-methoxyphenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitors SHP099 and SHP244 | PDB:6BMU | ||||
| Method | X-ray diffraction | Resolution | 2.12 Å | Mutation | No | [8] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSNPGDFTLS44 VRRNGAVTHI54 KIQNTGDYYD 64 LYGGEKFATL74 AELVQYYMEH84 HGQLKGDVIE97 LKYPLNCADP107 TSERWFHGHL 117 EKLLTEKGKH132 GSFLVRESPG145 DFVLSVRTGS165 KVTHVMIRCQ175 ELKYDVGGGE 185 RFDSLTDLVE195 HYKKNPMVET205 LGTVLQLKQP215 LNTTRINAAE225 IESRVRELSK 235 LQGFWEEFET253 LQQQECKLLY263 SRKEGQRQEN273 KNKNRYKNIL283 PFDHTRVVLH 293 DGDPPVSDYI305 NANIIMPPKK325 SYIATQGCLQ335 NTVNDFWRMV345 FQENSRVIVM 355 TTKEVERGKS365 KCVKYWPDEY375 ALKEYGVMRV385 RNVKESAAHD395 YTLRELKLSK 405 VGQGNTERTV415 WQYHFRTWPD425 HGVPSDPGGV435 LDFLEEVHHK445 QESIMDAGPV 455 VVHCSAGIGR465 TGTFIVIDIL475 IDIIREKGVD485 CDIDVPKTIQ495 MVRSQRSGMV 505 QTEAQYRFIY515 MAVQHYIETL525
|
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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 .DZV or .DZV2 or .DZV3 or :3DZV;style chemicals stick;color identity;select .A:79 or .A:80 or .A:83 or .A:84 or .A:262 or .A:263 or .A:264 or .A:265 or .A:266 or .A:269 or .A:280 or .A:281 or .A:282 or .A:283; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 6-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-[3-chloro-2-(cyclopropylamino)pyridin-4-yl]-5-methyl-2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Pyrazolo-pyrimidinone 1 SHP389 | PDB:6MDC | ||||
| Method | X-ray diffraction | Resolution | 2.14 Å | Mutation | No | [9] |
| PDB Sequence |
RRWFHPNITG
13 VEAENLLLTR23 GVDGSFLARP33 SKSNPGDFTL43 SVRRNGAVTH53 IKIQNTGDYY 63 DLYGGEKFAT73 LAELVQYYME83 HIELKYPLNC104 ADPTSERWFH114 GHLSGKEAEK 124 LLTEKGKHGS134 FLVRESGDFV148 LSVRTGDSKV167 THVMIRCQEL177 KYDVGGGERF 187 DSLTDLVEHY197 KKNPMVETLG207 TVLQLKQPLN217 TTRINAAEIE227 SRVRELSKLQ 245 GFWEEFETLQ255 QQECKLLYSR265 KEGQRQENKN275 KNRYKNILPF285 DHTRVVLHDG 295 DPNEPVSDYI305 NANIIMPEFK322 PKKSYIATQG332 CLQNTVNDFW342 RMVFQENSRV 352 IVMTTKEVER362 GKSKCVKYWP372 DEYALKEYGV382 MRVRNVKESA392 AHDYTLRELK 402 LSKVGQGNTE412 RTVWQYHFRT422 WPDHGVPSDP432 GGVLDFLEEV442 HHKQESIMDA 452 GPVVVHCSAG462 IGRTGTFIVI472 DILIDIIREK482 GVDCDIDVPK492 TIQMVRSQRS 502 GMVQTEAQYR512 FIYMAVQHYI522 ETL
|
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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 .JEA or .JEA2 or .JEA3 or :3JEA;style chemicals stick;color identity;select .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:112 or .A:113 or .A:114 or .A:115 or .A:216 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495 or .A:511; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO107
4.808
THR108
2.705
SER109
4.480
GLU110
2.804
ARG111
2.885
TRP112
4.970
PHE113
2.800
HIS114
3.801
GLY115
4.251
LEU216
3.455
ASN217
4.948
THR218
3.804
|
|||||
| Ligand Name: 3-(4-bromophenyl)-4-(4-methylphenyl)-1H-pyrazolo[3,4-b]pyridine-6-carboxylic acid | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Pyrazolo-pyridine 4 | PDB:6MDA | ||||
| Method | X-ray diffraction | Resolution | 2.21 Å | Mutation | No | [9] |
| PDB Sequence |
RRWFHPNITG
13 VEAENLLLTR23 GVDGSFLARP33 SNPGDFTLSV45 RRNGAVTHIK55 IQNTGDYYDL 65 YGGEKFATLA75 ELVQYYMEHI96 ELKYPLNCAD106 PTSERWFHGH116 LSGKEAEKLL 126 TEKGKHGSFL136 VREPGDFVLS150 VRTGDSKVTH169 VMIRCQELKY179 DVGGGERFDS 189 LTDLVEHYKK199 NPMVETLGTV209 LQLKQPLNTT219 RINAAEIESR229 VRELSKLQGF 247 WEEFETLQQQ257 ECKLLYSRKE267 GQRQENKNKN277 RYKNILPFDH287 TRVVLHSDYI 305 NANIIMPKSY327 IATQGCLQNT337 VNDFWRMVFQ347 ENSRVIVMTT357 KEVERGKSKC 367 VKYWPDEYAL377 KEYGVMRVRN387 VKESAAHDYT397 LRELKLSKVG407 QGNTERTVWQ 417 YHFRTWPDHG427 VPSDPGGVLD437 FLEEVHHKQE447 SIMDAGPVVV457 HCSAGIGRTG 467 TFIVIDILID477 IIREKGVDCD487 IDVPKTIQMV497 RSQRSGMVQT507 EAQYRFIYMA 517 VQHYIETL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .JED or .JED2 or .JED3 or :3JED;style chemicals stick;color identity;select .A:110 or .A:111 or .A:113 or .A:114 or .A:215 or .A:216 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:251 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495 or .A:511; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLU110
4.719
ARG111
2.753
PHE113
3.343
HIS114
3.394
PRO215
4.379
LEU216
3.643
ASN217
3.009
THR218
3.345
THR219
3.269
GLU249
3.790
|
|||||
| Ligand Name: 3-Benzyl-8-chloro-2-hydroxypyrimido[2,1-b][1,3]benzothiazol-4-one | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 F285S in Complex with Allosteric Inhibitor JLR-2 | PDB:6BN5 | ||||
| Method | X-ray diffraction | Resolution | 2.22 Å | Mutation | Yes | [11] |
| PDB Sequence |
WFHPNITGVE
15 AENLLLTRGV25 DGSFLARPSD40 FTLSVRAVTH53 IKIQNTGDYY63 DLYGGEKFAT 73 LAELVQYYME83 HIELKYPLNC104 ADPTSERWFH114 GHLSGKEAEK124 LLTHGSFLVR 138 EPGDFVLSVR152 TGDSKVTHVM171 IRCQELKYDV181 GGGERFDSLT191 DLVEHYKKNP 201 MVETLGTVLQ211 LKQPNTTRIN222 AAIESRVREL233 SQGFWEEFET253 LQQQECKLLY 263 SRKEGQRQEN273 KNKNRYKNIL283 PSDHTRVVLH293 SDYINANIIM311 PKSYIATQGC 333 LQNTVNDFWR343 MVFQENSRVI353 VMTTKEVERG363 KSKCVKYWPD373 EYALKEYGVM 383 RVRNVKESAA393 HDYTLRELKL403 SKVGQGNTER413 TVWQYHFRTW423 PDHGVPSDPG 433 GVLDFLEEVH443 HKQESIMDAG453 PVVVHCSAGI463 GRTGTFIVID473 ILIDIIREKG 483 VDCDIDVPKT493 IQMVRSQRSG503 MVQTEAQYRF513 IYMAVQHY
|
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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 .DZJ or .DZJ2 or .DZJ3 or :3DZJ;style chemicals stick;color identity;select .A:111 or .A:217 or .A:219 or .A:250 or .A:253 or .A:254 or .A:257 or .A:261 or .A:489 or .A:491 or .A:492 or .A:495 or .A:496 or .A:499; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)-5-methyl-2H-pyrazolo[3,4-d]pyrimidin-4-one | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Pyrazolo-pyrimidinone 5 | PDB:6MDB | ||||
| Method | X-ray diffraction | Resolution | 2.34 Å | Mutation | No | [7] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHHGQLKGDV95 IELKYPLNCA105 DPTSERWFHG 115 HLSGKEAEKL125 LTEKGKHGSF135 LVRESQPGDF147 VLSVRTGDSK166 VTHVMIRCQE 176 LKYDVGGGER186 FDSLTDLVEH196 YKKNPMVETL206 GTVLQLKQPL216 NTTRINAAEI 226 ESRVRELSKL236 QGFWEEFETL254 QQQECKLLYS264 RKEGQRQENK274 NKNRYKNILP 284 FDHTRVVLHD294 GDPPVSDYIN306 ANIIMPKSYI328 ATQGCLQNTV338 NDFWRMVFQE 348 NSRVIVMTTK358 EVERGKSKCV368 KYWPDEYALK378 EYGVMRVRNV388 KESAAHDYTL 398 RELKLSKVGQ408 GNTERTVWQY418 HFRTWPDHGV428 PSDPGGVLDF438 LEEVHHKQES 448 IMDAGPVVVH458 CSAGIGRTGT468 FIVIDILIDI478 IREKGVDCDI488 DVPKTIQMVR 498 SQRSGMVQTE508 AQYRFIYMAV518 QHYIETL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .JE4 or .JE42 or .JE43 or :3JE4;style chemicals stick;color identity;select .A:108 or .A:110 or .A:111 or .A:113 or .A:114 or .A:216 or .A:218 or .A:219 or .A:249 or .A:250 or .A:251 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: [3-[(3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-6-(2,3-dichlorophenyl)-5-methylpyrazin-2-yl]methanol | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor RMC-4550 | PDB:7RCT | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [12] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHHGQLKENG93 DVIELKYPLN103 CADPTSERWF 113 HGHLSGKEAE123 KLLTEKGKHG133 SFLVRESQSH143 PGDFVLSVRT153 GDDKNDGKSK 166 VTHVMIRCQE176 LKYDVGGGER186 FDSLTDLVEH196 YKKNPMVETL206 GTVLQLKQPL 216 NTTRINAAEI226 ESRVRELSKL236 QGFWEEFETL254 QQQECKLLYS264 RKEGQRQENK 274 NKNRYKNILP284 FDHTRVVLHD294 GDPNEPVSDY304 INANIIMPEK324 KSYIATQGCL 334 QNTVNDFWRM344 VFQENSRVIV354 MTTKEVERGK364 SKCVKYWPDE374 YALKEYGVMR 384 VRNVKESAAH394 DYTLRELKLS404 KVGQGNTERT414 VWQYHFRTWP424 DHGVPSDPGG 434 VLDFLEEVHH444 KQESIMDAGP454 VVVHCSAGIG464 RTGTFIVIDI474 LIDIIREKGV 484 DCDIDVPKTI494 QMVRSQRSGM504 VQTEAQYRFI514 YMAVQHYIET524 L |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .4Q4 or .4Q42 or .4Q43 or :34Q4;style chemicals stick;color identity;select .B:107 or .B:108 or .B:109 or .B:110 or .B:111 or .B:113 or .B:114 or .B:216 or .B:217 or .B:218 or .B:219 or .B:249 or .B:250 or .B:253 or .B:254 or .B:257 or .B:489 or .B:491 or .B:492 or .B:495 or .B:511; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO107
4.580
THR108
2.509
SER109
4.431
GLU110
3.005
ARG111
3.128
PHE113
2.789
HIS114
3.742
LEU216
2.999
ASN217
3.413
THR218
3.136
THR219
3.441
|
|||||
| Ligand Name: 6-(4-Amino-4-methylpiperidin-1-yl)-3-[(2,3-dichlorophenyl)sulfanyl]pyrazin-2-amine | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor Compound 24 | PDB:7JVN | ||||
| Method | X-ray diffraction | Resolution | 1.92 Å | Mutation | No | [13] |
| PDB Sequence |
RRWFHPNITG
13 VEAENLLLTR23 GVDGSFLARP33 SNPGDFTLSV45 RRNGAVTHIK55 IQNTGDYYDL 65 YGGEKFATLA75 ELVQYYMEHG86 QLKIELKYPL102 NCADPTSERW112 FHGHLSGKEA 122 EKLLTEKGKH132 GSFLVREPGD146 FVLSVRTGDS165 KVTHVMIRCQ175 ELKYDVGGGE 185 RFDSLTDLVE195 HYKKNPMVET205 LGTVLQLKQP215 LNTTRINAAE225 IESRVRELSK 235 LQGFWEEFET253 LQQQECKLLY263 SRKEGQRQEN273 KNKNRYKNIL283 PFDHTRVVLH 293 DGDPSDYINA307 NIIMPKSYIA329 TQGCLQNTVN339 DFWRMVFQEN349 SRVIVMTTKE 359 VERGKSKCVK369 YWPDEYALKE379 YGVMRVRNVK389 ESAAHDYTLR399 ELKLSKVGQG 409 NTERTVWQYH419 FRTWPDHGVP429 SDPGGVLDFL439 EEVHHKQESI449 MDAGPVVVHC 459 SAGIGRTGTF469 IVIDILIDII479 REKGVDCDID489 VPKTIQMVRS499 QRSGMVQTEA 509 QYRFIYMAVQ519 HYIETL
|
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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 .VKP or .VKP2 or .VKP3 or :3VKP;style chemicals stick;color identity;select .A:108 or .A:110 or .A:111 or .A:112 or .A:113 or .A:114 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:251 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495 or .A:511; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
THR108
3.941
GLU110
3.872
ARG111
2.931
TRP112
4.950
PHE113
2.810
HIS114
3.747
ASN217
3.893
THR218
3.645
THR219
3.530
GLU249
2.909
|
|||||
| Ligand Name: Batoprotafib | Ligand Info | |||||
| Structure Description | Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor TNO155 | PDB:7JVM | ||||
| Method | X-ray diffraction | Resolution | 2.17 Å | Mutation | No | [13] |
| PDB Sequence |
SRRWFHPNIT
12 GVEAENLLLT22 RGVDGSFLAR32 PSKSNPGDFT42 LSVRRNGAVT52 HIKIQNTGDY 62 YDLYGGEKFA72 TLAELVQYYM82 EHHGQLKDVI96 ELKYPLNCAD106 PTSERWFHGH 116 LSGKEAEKLL126 TEKGKHGSFL136 VRESPGDFVL149 SVRTGDSKVT168 HVMIRCQELK 178 YDVGGGERFD188 SLTDLVEHYK198 KNPMVETLGT208 VLQLKQPLNT218 TRINAAEIES 228 RVRELSKLQG246 FWEEFETLQQ256 QECKLLYSRK266 EGQRQENKNK276 NRYKNILPFD 286 HTRVVLHDGD296 PPVSDYINAN308 IIMPEKSYIA329 TQGCLQNTVN339 DFWRMVFQEN 349 SRVIVMTTKE359 VERGKSKCVK369 YWPDEYALKE379 YGVMRVRNVK389 ESAAHDYTLR 399 ELKLSKVGQG409 NTERTVWQYH419 FRTWPDHGVP429 SDPGGVLDFL439 EEVHHKQESI 449 MDAGPVVVHC459 SAGIGRTGTF469 IVIDILIDII479 REKGVDCDID489 VPKTIQMVRS 499 QRSGMVQTEA509 QYRFIYMAVQ519 HYIETL
|
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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 .VKS or .VKS2 or .VKS3 or :3VKS;style chemicals stick;color identity;select .A:107 or .A:108 or .A:109 or .A:110 or .A:111 or .A:113 or .A:114 or .A:217 or .A:218 or .A:219 or .A:249 or .A:250 or .A:251 or .A:253 or .A:254 or .A:257 or .A:489 or .A:491 or .A:492 or .A:495 or .A:511; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PRO107
4.716
THR108
2.628
SER109
4.441
GLU110
2.747
ARG111
3.041
PHE113
2.722
HIS114
3.702
ASN217
3.938
THR218
3.634
THR219
3.474
GLU249
3.776
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| Ligand Name: D-malate | Ligand Info | |||||
| Structure Description | Crystal structure of the human tyrosine phosphatase SHP2 (PTPN11) with an accessible active site | PDB:3B7O | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [14] |
| PDB Sequence |
GFWEEFETLQ
255 QQECKLLYSR265 KEGQRQENKN275 KNRYKNILPF285 DHTRVVLHDG295 DPNEPVSDYI 305 NANIIMPEKS326 YIATQGCLQN336 TVNDFWRMVF346 QENSRVIVMT356 TKEVERGKSK 366 CVKYWPDEYA376 LKEYGVMRVR386 NVKESAAHDY396 TLRELKLSKV406 GQGNTERTVW 416 QYHFRTWPDH426 GVPSDPGGVL436 DFLEEVHHKQ446 ESIMDAGPVV456 VHCSAGIGRT 466 GTFIVIDILI476 DIIREKGVDC486 DIDVPKTIQM496 VRSQRSGMVQ506 TEAQYRFIYM 516 AVQHYIETLQ526 RR
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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 .MLT or .MLT2 or .MLT3 or :3MLT;style chemicals stick;color identity;select .A:279 or .A:357 or .A:366 or .A:423 or .A:427 or .A:459 or .A:460 or .A:461 or .A:462 or .A:463 or .A:464 or .A:465 or .A:466 or .A:507 or .A:510; 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-[3-({4-[(1,3-Benzodioxol-5-Ylmethyl)amino]-4-Oxobutanoyl}amino)phenyl]-6-Hydroxy-3-Iodo-1-Methyl-1h-Indole-5-Carboxylic Acid | Ligand Info | |||||
| Structure Description | Crystal structure of protein tyrosine phosphatase Shp2 catalytic domain complex with small molecular compound L88N79 | PDB:4PVG | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [15] |
| PDB Sequence |
FETLQQQECK
260 LLYSRKEGQR270 QENKNKNRYK280 NILPFDHTRV290 VLHDGDPNEP300 VSDYINANII 310 MPEKSYIATQ331 GCLQNTVNDF341 WRMVFQENSR351 VIVMTTKEVE361 RGKSKCVKYW 371 PDEYALKEYG381 VMRVRNVKES391 AAHDYTLREL401 KLSKVGQGNT411 ERTVWQYHFR 421 TWPDHGVPSD431 PGGVLDFLEE441 VHHKQESIMD451 AGPVVVHCSA461 GIGRTGTFIV 471 IDILIDIIRE481 KGVDCDIDVP491 KTIQMVRSQR501 SGMVQTEAQY511 RFIYMAVQHY 521 IETL
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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 .2WT or .2WT2 or .2WT3 or :32WT;style chemicals stick;color identity;select .A:279 or .A:362 or .A:364 or .A:423 or .A:459 or .A:460 or .A:461 or .A:462 or .A:463 or .A:464 or .A:465 or .A:466 or .A:506 or .A:507 or .A:510; 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-{1-[3-(biphenyl-4-ylamino)-3-oxopropyl]-1H-1,2,3-triazol-4-yl}-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid | Ligand Info | |||||
| Structure Description | Crystal structure of the oncogenic tyrosine phosphatase SHP2 complexed with a salicylic acid-based small molecule inhibitor | PDB:3O5X | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [16] |
| PDB Sequence |
LYSRKEGQRQ
271 ENKNKNRYKN281 ILPFDHTRVV291 LHDGDPNEPV301 SDYINANIIM311 PKKSYIATQG 332 CLQNTVNDFW342 RMVFQENSRV352 IVMTTKEVER362 GKSKCVKYWP372 DEYALKEYGV 382 MRVRNVKESA392 AHDYTLRELK402 LSKVGQGNTE412 RTVWQYHFRT422 WPDHGVPSDP 432 GGVLDFLEEV442 HHKQESIMDA452 GPVVVHCSAG462 IGRTGTFIVI472 DILIDIIREK 482 GVDCDIDVPK492 TIQMVRSQRS502 GMVQTEAQYR512 FIYMAVQHYI522 ETLQR |
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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 .JZG or .JZG2 or .JZG3 or :3JZG;style chemicals stick;color identity;select .A:279 or .A:361 or .A:362 or .A:364 or .A:366 or .A:423 or .A:426 or .A:427 or .A:459 or .A:460 or .A:461 or .A:464 or .A:465 or .A:466 or .A:506 or .A:510; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Ca-15,17-dien-1-yl]oxy}-1-hydroxy-3-oxopropyl]-3-methylbut-2-enedioic acid | Ligand Info | |||||
| Structure Description | Crystal structure of SHP2 in complex with a tautomycetin analog TTN D-1 | PDB:3MOW | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [17] |
| PDB Sequence |
LYSRKEGQRQ
271 ENKNKNRYKN281 ILPFDHTRVV291 LHDGDPNEPV301 SDYINANIIM311 PEKSYIATQG 332 CLQNTVNDFW342 RMVFQENSRV352 IVMTTKEVER362 GKSKCVKYWP372 DEYALKEYGV 382 MRVRNVKESA392 AHDYTLRELK402 LSKVGQGNTE412 RTVWQYHFRT422 WPDHGVPSDP 432 GGVLDFLEEV442 HHKQESIMDA452 GPVVVHCSAG462 IGRTGTFIVI472 DILIDIIREK 482 GVDCDIDVPK492 TIQMVRSQRS502 GMVQTEAQYR512 FIYMAVQHYI522 ETLQ |
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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 .B2B or .B2B2 or .B2B3 or :3B2B;style chemicals stick;color identity;select .A:278 or .A:279 or .A:282 or .A:334 or .A:335 or .A:364 or .A:365 or .A:366 or .A:368 or .A:459 or .A:460 or .A:461 or .A:462 or .A:463 or .A:464 or .A:465 or .A:506 or .A:510; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Idinium | Ligand Info | |||||
| Structure Description | Co-crystal structure of SHP2 in complex with a Cefsulodin derivative | PDB:4RDD | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [18] |
| PDB Sequence |
LYSRKEGQRQ
271 ENKNKNRYKN281 ILPFDHTRVV291 LHDGDPNEPV301 SDYINANIIM311 PEFETKCNNS 321 KPKKSYIATQ331 GCLQNTVNDF341 WRMVFQENSR351 VIVMTTKEVE361 RGKSKCVKYW 371 PDEYALKEYG381 VMRVRNVKES391 AAHDYTLREL401 KLSKVGQGNT411 ERTVWQYHFR 421 TWPDHGVPSD431 PGGVLDFLEE441 VHHKQESIMD451 AGPVVVHCSA461 GIGRTGTFIV 471 IDILIDIIRE481 KGVDCDIDVP491 KTIQMVRSQR501 SGMVQTEAQY511 RFIYMAVQHY 521 IETLQRR
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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 .3LU or .3LU2 or .3LU3 or :33LU;style chemicals stick;color identity;select .A:279 or .A:282 or .A:427 or .A:459 or .A:460 or .A:461 or .A:462 or .A:463 or .A:464 or .A:465 or .A:466 or .A:506 or .A:507 or .A:510; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structure of the tyrosine phosphatase SHP-2. Cell. 1998 Feb 20;92(4):441-50. | ||||
| REF 2 | Allosteric Inhibitors of SHP2 with Therapeutic Potential for Cancer Treatment. J Med Chem. 2017 Dec 28;60(24):10205-10219. | ||||
| REF 3 | Allosteric SHP2 Inhibitor, IACS-13909, Overcomes EGFR-Dependent and EGFR-Independent Resistance Mechanisms toward Osimertinib. Cancer Res. 2020 Nov 1;80(21):4840-4853. | ||||
| REF 4 | Discovery of 6-[(3S,4S)-4-Amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl]-3-(2,3-dichlorophenyl)-2-methyl-3,4-dihydropyrimidin-4-one (IACS-15414), a Potent and Orally Bioavailable SHP2 Inhibitor. J Med Chem. 2021 Oct 28;64(20):15141-15169. | ||||
| REF 5 | Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016 Jul 7;535(7610):148-52. | ||||
| REF 6 | Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82. | ||||
| REF 7 | 6-Amino-3-methylpyrimidinones as Potent, Selective, and Orally Efficacious SHP2 Inhibitors. J Med Chem. 2019 Feb 28;62(4):1793-1802. | ||||
| REF 8 | Dual Allosteric Inhibition of SHP2 Phosphatase. ACS Chem Biol. 2018 Mar 16;13(3):647-656. | ||||
| REF 9 | Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors. J Med Chem. 2019 Feb 28;62(4):1781-1792. | ||||
| REF 10 | SHP2 allosteric inhibitor TK-453 alleviates psoriasis-like skin inflammation in mice via inhibition of IL-23/Th17 axis. iScience. 2022 Mar 1;25(4):104009. | ||||
| REF 11 | Identification of an allosteric benzothiazolopyrimidone inhibitor of the oncogenic protein tyrosine phosphatase SHP2. Bioorg Med Chem. 2017 Dec 15;25(24):6479-6485. | ||||
| REF 12 | Targeted Degradation of the Oncogenic Phosphatase SHP2. Biochemistry. 2021 Aug 31;60(34):2593-2609. | ||||
| REF 13 | Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer. J Med Chem. 2020 Nov 25;63(22):13578-13594. | ||||
| REF 14 | Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 2009 Jan 23;136(2):352-63. | ||||
| REF 15 | Crystal structure of protein tyrosine Shp2 catalytic domain complex with compound L88N79 | ||||
| REF 16 | Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). J Med Chem. 2010 Mar 25;53(6):2482-93. | ||||
| REF 17 | Crystal structure of SHP2 in complex with a tautomycetin analog TTN D-1 | ||||
| REF 18 | Exploring the Existing Drug Space for Novel pTyr Mimetic and SHP2 Inhibitors. ACS Med Chem Lett. 2015 Jun 8;6(7):782-6. | ||||
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