Structure of PDB 6mdc Chain A Binding Site BS01

Receptor Information
>6mdc Chain A (length=483) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
RRWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTH
IKIQNTGDYYDLYGGEKFATLAELVQYYMEHIELKYPLNCADPTSERWFH
GHLSGKEAEKLLTEKGKHGSFLVRESGDFVLSVRTGDSKVTHVMIRCQEL
KYDVGGGERFDSLTDLVEHYKKNPMVETLGTVLQLKQPLNTTRINAAEIE
SRVRELSKLQGFWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKNILPF
DHTRVVLHDGDPNEPVSDYINANIIMPEFKPKKSYIATQGCLQNTVNDFW
RMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESA
AHDYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEV
HHKQESIMDAGPVVVHCSAGIGRTGTFIVIDILIDIIREKGVDCDIDVPK
TIQMVRSQRSGMVQTEAQYRFIYMAVQHYIETL
Ligand information
Ligand IDJEA
InChIInChI=1S/C23H29ClN8O2/c1-12-18(25)23(11-34-12)6-9-32(10-7-23)22-28-19-15(21(33)31(22)2)17(29-30-19)14-5-8-26-20(16(14)24)27-13-3-4-13/h5,8,12-13,18H,3-4,6-7,9-11,25H2,1-2H3,(H,26,27)(H,29,30)/t12-,18+/m0/s1
InChIKeyURUPFUYPXLMTMT-KPZWWZAWSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.6CC1C(C2(CCN(CC2)C3=Nc4c(c([nH]n4)c5ccnc(c5Cl)NC6CC6)C(=O)N3C)CO1)N
ACDLabs 12.01c12nnc(c1C(=O)N(C)C(=N2)N4CCC3(C(C(OC3)C)N)CC4)c5ccnc(c5Cl)NC6CC6
CACTVS 3.385C[C@@H]1OCC2(CCN(CC2)C3=Nc4n[nH]c(c5ccnc(NC6CC6)c5Cl)c4C(=O)N3C)[C@@H]1N
CACTVS 3.385C[CH]1OCC2(CCN(CC2)C3=Nc4n[nH]c(c5ccnc(NC6CC6)c5Cl)c4C(=O)N3C)[CH]1N
OpenEye OEToolkits 2.0.6C[C@H]1[C@H](C2(CCN(CC2)C3=Nc4c(c([nH]n4)c5ccnc(c5Cl)NC6CC6)C(=O)N3C)CO1)N
FormulaC23 H29 Cl N8 O2
Name6-[(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
ChEMBLCHEMBL4439006
DrugBank
ZINC
PDB chain6mdc Chain A Residue 601 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB6mdc Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors.
Resolution2.14 Å
Binding residue
(original residue number in PDB)		T108 E110 R111 F113 T219 E249 E250 T253 L254 Q257 P491 K492
Binding residue
(residue number reindexed from 1)		T94 E96 R97 F99 T192 E214 E215 T218 L219 Q222 P449 K450
Annotation score1
Binding affinityMOAD: ic50=0.036uM
PDBbind-CN: -logKd/Ki=7.44,IC50=0.036uM
Enzymatic activity
Catalytic site (original residue number in PDB) D425 C459 R465 T466 Q506
Catalytic site (residue number reindexed from 1) D383 C417 R423 T424 Q464
Enzyme Commision number 3.1.3.48: protein-tyrosine-phosphatase.
Gene Ontology
Molecular Function
GO:0004725 protein tyrosine phosphatase activity
Biological Process
GO:0006470 protein dephosphorylation
GO:0016311 dephosphorylation

View graph for
Molecular Function
View graph for
Biological Process
External links
PDB RCSB:6mdc, PDBe:6mdc, PDBj:6mdc
PDBsum6mdc
PubMed30688462
UniProtQ06124|PTN11_HUMAN Tyrosine-protein phosphatase non-receptor type 11 (Gene Name=PTPN11)

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