Structure of PDB 4ejn Chain A Binding Site BS01

Receptor Information
>4ejn Chain A (length=376) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
VAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPAPLNNFSVAQC
QLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGR
VTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVVLQNSRH
PFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEI
VSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKKTFCGT
PEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELIL
MEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIV
WQHVYEKKLSPPFKPQVTSETDTRYF
Ligand information
Ligand ID0R4
InChIInChI=1S/C33H26FN7O2/c1-20(42)38-25-8-3-5-22(18-25)28-14-15-29-32(39-28)41(31(40-29)27-9-4-16-36-30(27)35)26-12-10-21(11-13-26)19-37-33(43)23-6-2-7-24(34)17-23/h2-18H,19H2,1H3,(H2,35,36)(H,37,43)(H,38,42)
InChIKeyWFDHLKUQFQCHKF-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(=O)Nc1cccc(c1)c2ccc3c(n2)n(c(n3)c4cccnc4N)c5ccc(cc5)CNC(=O)c6cccc(c6)F
ACDLabs 12.01Fc1cccc(c1)C(=O)NCc2ccc(cc2)n4c5nc(ccc5nc4c3cccnc3N)c6cccc(NC(=O)C)c6
CACTVS 3.370CC(=O)Nc1cccc(c1)c2ccc3nc(n(c4ccc(CNC(=O)c5cccc(F)c5)cc4)c3n2)c6cccnc6N
FormulaC33 H26 F N7 O2
NameN-(4-{5-[3-(acetylamino)phenyl]-2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl}benzyl)-3-fluorobenzamide
ChEMBLCHEMBL2177836
DrugBank
ZINCZINC000095579760
PDB chain4ejn Chain A Residue 501 [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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PDB4ejn Discovery and optimization of a series of 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amines: orally bioavailable, selective, and potent ATP-independent Akt inhibitors.
Resolution2.19 Å
Binding residue
(original residue number in PDB)		N53 N54 Q59 Q79 W80 I84 L210 T211 V270 Y272 R273 I290 D292
Binding residue
(residue number reindexed from 1)		N43 N44 Q49 Q69 W70 I74 L153 T154 V213 Y215 R216 I233 D235
Annotation score1
Binding affinityMOAD: ic50=0.005uM
PDBbind-CN: -logKd/Ki=8.30,IC50=5nM
BindingDB: IC50=44nM
Enzymatic activity
Catalytic site (original residue number in PDB) D274 K276 N279 D292 T312
Catalytic site (residue number reindexed from 1) D217 K219 N222 D235 T250
Enzyme Commision number 2.7.11.1: non-specific serine/threonine protein kinase.
Gene Ontology
Molecular Function
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004712 protein serine/threonine/tyrosine kinase activity
GO:0005515 protein binding
GO:0005516 calmodulin binding
GO:0005524 ATP binding
GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding
GO:0016301 kinase activity
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0030235 nitric-oxide synthase regulator activity
GO:0030291 protein serine/threonine kinase inhibitor activity
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043325 phosphatidylinositol-3,4-bisphosphate binding
GO:0044024 histone H2AS1 kinase activity
GO:0071889 14-3-3 protein binding
GO:0099104 potassium channel activator activity
GO:0106310 protein serine kinase activity
Biological Process
GO:0001649 osteoblast differentiation
GO:0001893 maternal placenta development
GO:0001934 positive regulation of protein phosphorylation
GO:0001938 positive regulation of endothelial cell proliferation
GO:0002042 cell migration involved in sprouting angiogenesis
GO:0003376 sphingosine-1-phosphate receptor signaling pathway
GO:0005977 glycogen metabolic process
GO:0005978 glycogen biosynthetic process
GO:0005979 regulation of glycogen biosynthetic process
GO:0006006 glucose metabolic process
GO:0006338 chromatin remodeling
GO:0006417 regulation of translation
GO:0006468 protein phosphorylation
GO:0006469 negative regulation of protein kinase activity
GO:0006606 protein import into nucleus
GO:0006809 nitric oxide biosynthetic process
GO:0006915 apoptotic process
GO:0006924 activation-induced cell death of T cells
GO:0006954 inflammatory response
GO:0006979 response to oxidative stress
GO:0007165 signal transduction
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007186 G protein-coupled receptor signaling pathway
GO:0007281 germ cell development
GO:0007399 nervous system development
GO:0008283 cell population proliferation
GO:0008286 insulin receptor signaling pathway
GO:0008637 apoptotic mitochondrial changes
GO:0009408 response to heat
GO:0009725 response to hormone
GO:0010467 gene expression
GO:0010507 negative regulation of autophagy
GO:0010595 positive regulation of endothelial cell migration
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0010748 negative regulation of long-chain fatty acid import across plasma membrane
GO:0010761 fibroblast migration
GO:0010763 positive regulation of fibroblast migration
GO:0010765 positive regulation of sodium ion transport
GO:0010907 positive regulation of glucose metabolic process
GO:0010951 negative regulation of endopeptidase activity
GO:0010975 regulation of neuron projection development
GO:0016242 negative regulation of macroautophagy
GO:0016310 phosphorylation
GO:0016567 protein ubiquitination
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0019049 virus-mediated perturbation of host defense response
GO:0019221 cytokine-mediated signaling pathway
GO:0022605 mammalian oogenesis stage
GO:0030154 cell differentiation
GO:0030163 protein catabolic process
GO:0030307 positive regulation of cell growth
GO:0030334 regulation of cell migration
GO:0030335 positive regulation of cell migration
GO:0031295 T cell costimulation
GO:0031397 negative regulation of protein ubiquitination
GO:0031641 regulation of myelination
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0031929 TOR signaling
GO:0031999 negative regulation of fatty acid beta-oxidation
GO:0032079 positive regulation of endodeoxyribonuclease activity
GO:0032091 negative regulation of protein binding
GO:0032094 response to food
GO:0032287 peripheral nervous system myelin maintenance
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032869 cellular response to insulin stimulus
GO:0032880 regulation of protein localization
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0034405 response to fluid shear stress
GO:0035556 intracellular signal transduction
GO:0035655 interleukin-18-mediated signaling pathway
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0036294 cellular response to decreased oxygen levels
GO:0042593 glucose homeostasis
GO:0042981 regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043276 anoikis
GO:0043488 regulation of mRNA stability
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO:0043536 positive regulation of blood vessel endothelial cell migration
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045600 positive regulation of fat cell differentiation
GO:0045725 positive regulation of glycogen biosynthetic process
GO:0045737 positive regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0045746 negative regulation of Notch signaling pathway
GO:0045861 negative regulation of proteolysis
GO:0045944 positive regulation of transcription by RNA polymerase II
GO:0046326 positive regulation of D-glucose import
GO:0046622 positive regulation of organ growth
GO:0046777 protein autophosphorylation
GO:0046889 positive regulation of lipid biosynthetic process
GO:0048009 insulin-like growth factor receptor signaling pathway
GO:0048266 behavioral response to pain
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0051000 positive regulation of nitric-oxide synthase activity
GO:0051091 positive regulation of DNA-binding transcription factor activity
GO:0051146 striated muscle cell differentiation
GO:0051247 positive regulation of protein metabolic process
GO:0060079 excitatory postsynaptic potential
GO:0060416 response to growth hormone
GO:0060644 mammary gland epithelial cell differentiation
GO:0060709 glycogen cell differentiation involved in embryonic placenta development
GO:0060716 labyrinthine layer blood vessel development
GO:0070141 response to UV-A
GO:0070848 response to growth factor
GO:0071356 cellular response to tumor necrosis factor
GO:0071363 cellular response to growth factor stimulus
GO:0071364 cellular response to epidermal growth factor stimulus
GO:0071380 cellular response to prostaglandin E stimulus
GO:0071901 negative regulation of protein serine/threonine kinase activity
GO:0072655 establishment of protein localization to mitochondrion
GO:0072656 maintenance of protein location in mitochondrion
GO:0072752 cellular response to rapamycin
GO:0090201 negative regulation of release of cytochrome c from mitochondria
GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus
GO:0097194 execution phase of apoptosis
GO:0099175 regulation of postsynapse organization
GO:0110002 regulation of tRNA methylation
GO:0140052 cellular response to oxidised low-density lipoprotein particle stimulus
GO:0150033 negative regulation of protein localization to lysosome
GO:0160049 negative regulation of cGAS/STING signaling pathway
GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
GO:1900182 positive regulation of protein localization to nucleus
GO:1901653 cellular response to peptide
GO:1901796 regulation of signal transduction by p53 class mediator
GO:1902018 negative regulation of cilium assembly
GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:1903038 negative regulation of leukocyte cell-cell adhesion
GO:1903078 positive regulation of protein localization to plasma membrane
GO:1903318 negative regulation of protein maturation
GO:1904263 positive regulation of TORC1 signaling
GO:1905552 positive regulation of protein localization to endoplasmic reticulum
GO:1990090 cellular response to nerve growth factor stimulus
GO:1990418 response to insulin-like growth factor stimulus
GO:2000010 positive regulation of protein localization to cell surface
GO:2000074 regulation of type B pancreatic cell development
GO:2000402 negative regulation of lymphocyte migration
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005758 mitochondrial intermembrane space
GO:0005819 spindle
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005911 cell-cell junction
GO:0005938 cell cortex
GO:0015630 microtubule cytoskeleton
GO:0016020 membrane
GO:0030027 lamellipodium
GO:0031982 vesicle
GO:0032991 protein-containing complex
GO:0036064 ciliary basal body
GO:0098794 postsynapse
GO:0098978 glutamatergic synapse

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Molecular Function
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Biological Process
View graph for
Cellular Component
External links
PDB RCSB:4ejn, PDBe:4ejn, PDBj:4ejn
PDBsum4ejn
PubMed22533986
UniProtP31749|AKT1_HUMAN RAC-alpha serine/threonine-protein kinase (Gene Name=AKT1)

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