Structure of PDB 3p78 Chain A Binding Site BS01

Receptor Information
>3p78 Chain A (length=332) Species: 10090 (Mus musculus) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
RPTFYRQELNKTIWEVPERYQNLSPVGSGSVCAAFDTKTGHRVAVKKLSR
PFQSIIHAKRTYRELRLLKHMKHENVIGLLDVFTPARSLEEFNDVYLVTH
LMGADLNNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLA
VNEDCELKILDFGATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGR
TLFPGTDHIDQLKLILRLVGTPGAELLKKISSESARNYIQSLAQMPKMNF
ANVFIGANPLAVDLLEKMLVLDSDKRITAAQALAHAYFAQYHDPDDEPVA
DPYDQSFESRDLLIDEWKSLTYDEVISFVPPP
Ligand information
Ligand IDP78
InChIInChI=1S/C24H27N3O4S2/c1-24(2,3)20-15-19(22(28)27-10-12-33(30,31)13-11-27)21(32-20)26-23(29)25-18-9-8-16-6-4-5-7-17(16)14-18/h4-9,14-15H,10-13H2,1-3H3,(H2,25,26,29)
InChIKeyAKQQWIZLJKLJED-UHFFFAOYSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01O=C(Nc2sc(cc2C(=O)N1CCS(=O)(=O)CC1)C(C)(C)C)Nc4cc3ccccc3cc4
CACTVS 3.370CC(C)(C)c1sc(NC(=O)Nc2ccc3ccccc3c2)c(c1)C(=O)N4CC[S](=O)(=O)CC4
OpenEye OEToolkits 1.7.0CC(C)(C)c1cc(c(s1)NC(=O)Nc2ccc3ccccc3c2)C(=O)N4CCS(=O)(=O)CC4
FormulaC24 H27 N3 O4 S2
Name1-{5-tert-butyl-3-[(1,1-dioxidothiomorpholin-4-yl)carbonyl]thiophen-2-yl}-3-naphthalen-2-ylurea
ChEMBLCHEMBL1929196
DrugBank
ZINCZINC000035922339
PDB chain3p78 Chain A Residue 362 [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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PDB3p78 Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).
Resolution2.3 Å
Binding residue
(original residue number in PDB)		A51 K53 E71 L75 I84 L104 T106 H148 L167 D168 F169
Binding residue
(residue number reindexed from 1)		A44 K46 E64 L68 I77 L97 T99 H141 L160 D161 F162
Annotation score1
Binding affinityMOAD: ic50=0.11uM
PDBbind-CN: -logKd/Ki=6.96,IC50=0.11uM
Enzymatic activity
Catalytic site (original residue number in PDB) D150 K152 N155 D168 T185
Catalytic site (residue number reindexed from 1) D143 K145 N148 D161 T165
Enzyme Commision number 2.7.11.24: mitogen-activated protein kinase.
Gene Ontology
Molecular Function
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:0016301 kinase activity
GO:0019899 enzyme binding
GO:0019903 protein phosphatase binding
GO:0048273 mitogen-activated protein kinase p38 binding
GO:0051525 NFAT protein binding
GO:0106310 protein serine kinase activity
Biological Process
GO:0000077 DNA damage checkpoint signaling
GO:0000165 MAPK cascade
GO:0000902 cell morphogenesis
GO:0001502 cartilage condensation
GO:0001525 angiogenesis
GO:0001649 osteoblast differentiation
GO:0001890 placenta development
GO:0002021 response to dietary excess
GO:0002062 chondrocyte differentiation
GO:0006006 glucose metabolic process
GO:0006355 regulation of DNA-templated transcription
GO:0006357 regulation of transcription by RNA polymerase II
GO:0006366 transcription by RNA polymerase II
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0006974 DNA damage response
GO:0007178 cell surface receptor protein serine/threonine kinase signaling pathway
GO:0007519 skeletal muscle tissue development
GO:0010628 positive regulation of gene expression
GO:0010831 positive regulation of myotube differentiation
GO:0016310 phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0019395 fatty acid oxidation
GO:0030278 regulation of ossification
GO:0030316 osteoclast differentiation
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031281 positive regulation of cyclase activity
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032495 response to muramyl dipeptide
GO:0032496 response to lipopolysaccharide
GO:0032735 positive regulation of interleukin-12 production
GO:0032868 response to insulin
GO:0035331 negative regulation of hippo signaling
GO:0035556 intracellular signal transduction
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0035994 response to muscle stretch
GO:0038066 p38MAPK cascade
GO:0042307 positive regulation of protein import into nucleus
GO:0042770 signal transduction in response to DNA damage
GO:0045648 positive regulation of erythrocyte differentiation
GO:0045663 positive regulation of myoblast differentiation
GO:0045944 positive regulation of transcription by RNA polymerase II
GO:0046323 D-glucose import
GO:0046326 positive regulation of D-glucose import
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048863 stem cell differentiation
GO:0051146 striated muscle cell differentiation
GO:0051403 stress-activated MAPK cascade
GO:0060045 positive regulation of cardiac muscle cell proliferation
GO:0060348 bone development
GO:0071222 cellular response to lipopolysaccharide
GO:0071223 cellular response to lipoteichoic acid
GO:0071356 cellular response to tumor necrosis factor
GO:0071479 cellular response to ionizing radiation
GO:0071493 cellular response to UV-B
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0090336 positive regulation of brown fat cell differentiation
GO:0090400 stress-induced premature senescence
GO:0098586 cellular response to virus
GO:0099179 regulation of synaptic membrane adhesion
GO:1900015 regulation of cytokine production involved in inflammatory response
GO:1901741 positive regulation of myoblast fusion
GO:2000379 positive regulation of reactive oxygen species metabolic process
Cellular Component
GO:0000922 spindle pole
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0016607 nuclear speck
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:3p78, PDBe:3p78, PDBj:3p78
PDBsum3p78
PubMed22014550
UniProtP47811|MK14_MOUSE Mitogen-activated protein kinase 14 (Gene Name=Mapk14)

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