Structure of PDB 4qtb Chain A Binding Site BS01

Receptor Information
>4qtb Chain A (length=351) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
VPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKI
SPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYIVQD
LMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLL
INTTCDLKICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYT
KSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCII
NMKARNYLQSLPSKTKVAWAKLFPKSDSKALDLLDRMLTFNPNKRITVEE
ALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERLKELIFQETARFQP
G
Ligand information
Ligand ID38Z
InChIInChI=1S/C33H33N9O2/c43-30(42-18-16-41(17-19-42)27-5-2-24(3-6-27)32-35-11-1-12-36-32)22-40-15-10-25(21-40)33(44)37-26-4-7-29-28(20-26)31(39-38-29)23-8-13-34-14-9-23/h1-9,11-14,20,25H,10,15-19,21-22H2,(H,37,44)(H,38,39)/t25-/m1/s1
InChIKeyHDAJDNHIBCDLQF-RUZDIDTESA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6c1cnc(nc1)c2ccc(cc2)N3CCN(CC3)C(=O)CN4CCC(C4)C(=O)Nc5ccc6c(c5)c([nH]n6)c7ccncc7
OpenEye OEToolkits 1.7.6c1cnc(nc1)c2ccc(cc2)N3CCN(CC3)C(=O)CN4CC[C@H](C4)C(=O)Nc5ccc6c(c5)c([nH]n6)c7ccncc7
CACTVS 3.385O=C(CN1CC[CH](C1)C(=O)Nc2ccc3n[nH]c(c4ccncc4)c3c2)N5CCN(CC5)c6ccc(cc6)c7ncccn7
CACTVS 3.385O=C(CN1CC[C@H](C1)C(=O)Nc2ccc3n[nH]c(c4ccncc4)c3c2)N5CCN(CC5)c6ccc(cc6)c7ncccn7
ACDLabs 12.01O=C(N3CCN(c2ccc(c1ncccn1)cc2)CC3)CN7CCC(C(=O)Nc5cc6c(c4ccncc4)nnc6cc5)C7
FormulaC33 H33 N9 O2
Name(3R)-1-(2-oxo-2-{4-[4-(pyrimidin-2-yl)phenyl]piperazin-1-yl}ethyl)-N-[3-(pyridin-4-yl)-2H-indazol-5-yl]pyrrolidine-3-carboxamide
ChEMBLCHEMBL3590107
DrugBank
ZINCZINC000096174209
PDB chain4qtb Chain A Residue 418 [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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PDB4qtb A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics.
Resolution1.4 Å
Binding residue
(original residue number in PDB)		A52 Y53 A69 K71 I73 Y81 R84 T85 E88 Q122 D123 M125 E126 T127 K131 L173 C183 D184
Binding residue
(residue number reindexed from 1)		A29 Y30 A46 K48 I50 Y58 R61 T62 E65 Q99 D100 M102 E103 T104 K108 L150 C160 D161
Annotation score1
Binding affinityMOAD: Kd=0.213uM
PDBbind-CN: -logKd/Ki=6.70,Kd~200nM
Enzymatic activity
Catalytic site (original residue number in PDB) D166 K168 S170 N171 D184 T207
Catalytic site (residue number reindexed from 1) D143 K145 S147 N148 D161 T184
Enzyme Commision number 2.7.11.24: mitogen-activated protein kinase.
Gene Ontology
Molecular Function
GO:0001784 phosphotyrosine residue binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004707 MAP kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0019902 phosphatase binding
GO:0042802 identical protein binding
GO:0106310 protein serine kinase activity
GO:0140297 DNA-binding transcription factor binding
Biological Process
GO:0000165 MAPK cascade
GO:0006351 DNA-templated transcription
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0006974 DNA damage response
GO:0008286 insulin receptor signaling pathway
GO:0009887 animal organ morphogenesis
GO:0010759 positive regulation of macrophage chemotaxis
GO:0014032 neural crest cell development
GO:0014044 Schwann cell development
GO:0016310 phosphorylation
GO:0019233 sensory perception of pain
GO:0030278 regulation of ossification
GO:0030509 BMP signaling pathway
GO:0030641 regulation of cellular pH
GO:0030878 thyroid gland development
GO:0031281 positive regulation of cyclase activity
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032206 positive regulation of telomere maintenance
GO:0032496 response to lipopolysaccharide
GO:0032872 regulation of stress-activated MAPK cascade
GO:0033554 cellular response to stress
GO:0034198 cellular response to amino acid starvation
GO:0035556 intracellular signal transduction
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0038133 ERBB2-ERBB3 signaling pathway
GO:0042473 outer ear morphogenesis
GO:0042552 myelination
GO:0042770 signal transduction in response to DNA damage
GO:0043330 response to exogenous dsRNA
GO:0045944 positive regulation of transcription by RNA polymerase II
GO:0048009 insulin-like growth factor receptor signaling pathway
GO:0048538 thymus development
GO:0050804 modulation of chemical synaptic transmission
GO:0051090 regulation of DNA-binding transcription factor activity
GO:0051216 cartilage development
GO:0051403 stress-activated MAPK cascade
GO:0051493 regulation of cytoskeleton organization
GO:0060020 Bergmann glial cell differentiation
GO:0060324 face development
GO:0060425 lung morphogenesis
GO:0060440 trachea formation
GO:0061308 cardiac neural crest cell development involved in heart development
GO:0070371 ERK1 and ERK2 cascade
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070498 interleukin-1-mediated signaling pathway
GO:0070849 response to epidermal growth factor
GO:0071260 cellular response to mechanical stimulus
GO:0071356 cellular response to tumor necrosis factor
GO:0072584 caveolin-mediated endocytosis
GO:0090170 regulation of Golgi inheritance
GO:0098792 xenophagy
GO:0120041 positive regulation of macrophage proliferation
GO:1904262 negative regulation of TORC1 signaling
GO:1904417 positive regulation of xenophagy
GO:2000641 regulation of early endosome to late endosome transport
Cellular Component
GO:0005634 nucleus
GO:0005635 nuclear envelope
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005769 early endosome
GO:0005770 late endosome
GO:0005788 endoplasmic reticulum lumen
GO:0005794 Golgi apparatus
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0005901 caveola
GO:0005925 focal adhesion
GO:0016020 membrane
GO:0031143 pseudopodium
GO:0070161 anchoring junction
GO:0098978 glutamatergic synapse

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4qtb, PDBe:4qtb, PDBj:4qtb
PDBsum4qtb
PubMed25195011
UniProtP27361|MK03_HUMAN Mitogen-activated protein kinase 3 (Gene Name=MAPK3)

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