Structure of PDB 6dcg Chain A Binding Site BS01

Receptor Information
>6dcg Chain A (length=326) Species: 10116 (Rattus norvegicus) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
VFDVGPRYTNLSYIGEGAYGMVCSAYDRVAIKKISPFEHQTYCQRTLREI
KILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQHLS
NDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLAR
VADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEML
SNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNK
VPWNRLFPNADSKALDLLDKMLTFNPHKRIEVEQALAHPYLEQYYDPSDE
PIAEAPFLPKEKLKELIFEETARFQP
Ligand information
Ligand IDG67
InChIInChI=1S/C37H41N9O3S/c1-24(2)49-32-12-9-28(20-38-32)34-30-19-29(10-11-31(30)41-42-34)40-36(48)37(50-4)15-18-45(22-37)21-33(47)46-16-13-26(14-17-46)25-5-7-27(8-6-25)35-39-23-44(3)43-35/h5-13,19-20,23-24H,14-18,21-22H2,1-4H3,(H,40,48)(H,41,42)/t37-/m0/s1
InChIKeyKPQQGHGDBBJGFA-QNGWXLTQSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01O=C(N1CCC(=CC1)c3ccc(c2nn(C)cn2)cc3)CN4CC(CC4)(SC)C(=O)Nc5cc6c(cc5)nnc6c7cnc(cc7)OC(C)C
OpenEye OEToolkits 2.0.6CC(C)Oc1ccc(cn1)c2c3cc(ccc3[nH]n2)NC(=O)[C@@]4(CCN(C4)CC(=O)N5CCC(=CC5)c6ccc(cc6)c7ncn(n7)C)SC
OpenEye OEToolkits 2.0.6CC(C)Oc1ccc(cn1)c2c3cc(ccc3[nH]n2)NC(=O)C4(CCN(C4)CC(=O)N5CCC(=CC5)c6ccc(cc6)c7ncn(n7)C)SC
CACTVS 3.385CS[C]1(CCN(CC(=O)N2CCC(=CC2)c3ccc(cc3)c4ncn(C)n4)C1)C(=O)Nc5ccc6[nH]nc(c7ccc(OC(C)C)nc7)c6c5
CACTVS 3.385CS[C@]1(CCN(CC(=O)N2CCC(=CC2)c3ccc(cc3)c4ncn(C)n4)C1)C(=O)Nc5ccc6[nH]nc(c7ccc(OC(C)C)nc7)c6c5
FormulaC37 H41 N9 O3 S
Name(3S)-3-(methylsulfanyl)-1-(2-{4-[4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl]-3,6-dihydropyridin-1(2H)-yl}-2-oxoethyl)-N-(3-{6-[(propan-2-yl)oxy]pyridin-3-yl}-1H-indazol-5-yl)pyrrolidine-3-carboxamide
ChEMBLCHEMBL4213970
DrugBank
ZINC
PDB chain6dcg Chain A Residue 403 [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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PDB6dcg MK-8353: Discovery of an Orally Bioavailable Dual Mechanism ERK Inhibitor for Oncology.
Resolution1.45 Å
Binding residue
(original residue number in PDB)		I29 A33 Y34 A50 K52 Y62 R65 E69 Q103 D104 L105 M106 E107 T108 K112 L154 D165
Binding residue
(residue number reindexed from 1)		I14 A18 Y19 A30 K32 Y42 R45 E49 Q83 D84 L85 M86 E87 T88 K92 L134 D145
Annotation score1
Binding affinityMOAD: ic50=7nM
PDBbind-CN: -logKd/Ki=8.15,IC50=7nM
Enzymatic activity
Catalytic site (original residue number in PDB) D147 K149 N152 D165 T188
Catalytic site (residue number reindexed from 1) D127 K129 N132 D145 T168
Enzyme Commision number 2.7.11.24: mitogen-activated protein kinase.
Gene Ontology
Molecular Function
GO:0001784 phosphotyrosine residue binding
GO:0003690 double-stranded DNA 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:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity
GO:0016301 kinase activity
GO:0019901 protein kinase binding
GO:0019902 phosphatase binding
GO:0031435 mitogen-activated protein kinase kinase kinase binding
GO:0042802 identical protein binding
GO:0106310 protein serine kinase activity
Biological Process
GO:0000165 MAPK cascade
GO:0006357 regulation of transcription by RNA polymerase II
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0006974 DNA damage response
GO:0007166 cell surface receptor signaling pathway
GO:0007507 heart development
GO:0008284 positive regulation of cell population proliferation
GO:0008286 insulin receptor signaling pathway
GO:0009636 response to toxic substance
GO:0009887 animal organ morphogenesis
GO:0010759 positive regulation of macrophage chemotaxis
GO:0014032 neural crest cell development
GO:0014044 Schwann cell development
GO:0015966 diadenosine tetraphosphate biosynthetic process
GO:0016310 phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0019233 sensory perception of pain
GO:0019858 cytosine metabolic process
GO:0030278 regulation of ossification
GO:0030335 positive regulation of cell migration
GO:0030521 androgen receptor signaling pathway
GO:0030641 regulation of cellular pH
GO:0030878 thyroid gland development
GO:0031647 regulation of protein stability
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032212 positive regulation of telomere maintenance via telomerase
GO:0032355 response to estradiol
GO:0032496 response to lipopolysaccharide
GO:0032872 regulation of stress-activated MAPK cascade
GO:0033574 response to testosterone
GO:0033598 mammary gland epithelial cell proliferation
GO:0034198 cellular response to amino acid starvation
GO:0034614 cellular response to reactive oxygen species
GO:0035094 response to nicotine
GO:0035556 intracellular signal transduction
GO:0036120 cellular response to platelet-derived growth factor stimulus
GO:0038127 ERBB signaling pathway
GO:0038133 ERBB2-ERBB3 signaling pathway
GO:0042220 response to cocaine
GO:0042307 positive regulation of protein import into nucleus
GO:0042473 outer ear morphogenesis
GO:0042542 response to hydrogen peroxide
GO:0042552 myelination
GO:0043330 response to exogenous dsRNA
GO:0043401 steroid hormone receptor signaling pathway
GO:0043627 response to estrogen
GO:0044849 estrous cycle
GO:0045596 negative regulation of cell differentiation
GO:0045727 positive regulation of translation
GO:0045893 positive regulation of DNA-templated transcription
GO:0046697 decidualization
GO:0048009 insulin-like growth factor receptor signaling pathway
GO:0048538 thymus development
GO:0050847 progesterone receptor signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0050853 B cell receptor signaling pathway
GO:0051403 stress-activated MAPK cascade
GO:0051493 regulation of cytoskeleton organization
GO:0060020 Bergmann glial cell differentiation
GO:0060045 positive regulation of cardiac muscle cell proliferation
GO:0060291 long-term synaptic potentiation
GO:0060324 face development
GO:0060425 lung morphogenesis
GO:0060440 trachea formation
GO:0060716 labyrinthine layer blood vessel development
GO:0061308 cardiac neural crest cell development involved in heart development
GO:0061431 cellular response to methionine
GO:0070371 ERK1 and ERK2 cascade
GO:0070849 response to epidermal growth factor
GO:0071276 cellular response to cadmium ion
GO:0071320 cellular response to cAMP
GO:0071356 cellular response to tumor necrosis factor
GO:0071364 cellular response to epidermal growth factor stimulus
GO:0071380 cellular response to prostaglandin E stimulus
GO:0072584 caveolin-mediated endocytosis
GO:0090170 regulation of Golgi inheritance
GO:0097237 cellular response to toxic substance
GO:0097305 response to alcohol
GO:0120041 positive regulation of macrophage proliferation
GO:1904355 positive regulation of telomere capping
GO:1990314 cellular response to insulin-like growth factor stimulus
GO:2000641 regulation of early endosome to late endosome transport
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005769 early endosome
GO:0005770 late endosome
GO:0005794 Golgi apparatus
GO:0005813 centrosome
GO:0005819 spindle
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0005901 caveola
GO:0005925 focal adhesion
GO:0014069 postsynaptic density
GO:0016020 membrane
GO:0030424 axon
GO:0031143 pseudopodium
GO:0032839 dendrite cytoplasm
GO:0032991 protein-containing complex
GO:0043204 perikaryon
GO:0070161 anchoring junction
GO:0072686 mitotic spindle

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:6dcg, PDBe:6dcg, PDBj:6dcg
PDBsum6dcg
PubMed30034615
UniProtP63086|MK01_RAT Mitogen-activated protein kinase 1 (Gene Name=Mapk1)

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