Structure of PDB 4ejn Chain A

Receptor sequence
>4ejnA (length=376) Species: 9606 (Homo sapiens) [Search protein sequence]
VAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPAPLNNFSVAQC
QLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGR
VTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVVLQNSRH
PFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEI
VSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKKTFCGT
PEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELIL
MEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIV
WQHVYEKKLSPPFKPQVTSETDTRYF
3D structure
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.
ChainA
Resolution2.19 Å
3D
structure
Catalytic site residues are labeled in the structure
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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.
Interaction with ligand
Site
#
Ligand Ligand
chain
Binding residues on receptor
(original residue number in PDB)
Binding residues on receptor
(residue number reindexed from 1)
Binding affinity
BS01 0R4 A N53 N54 Q59 Q79 W80 I84 L210 T211 V270 Y272 R273 I290 D292 N43 N44 Q49 Q69 W70 I74 L153 T154 V213 Y215 R216 I233 D235 MOAD: ic50=0.005uM
PDBbind-CN: -logKd/Ki=8.30,IC50=5nM
BindingDB: IC50=44nM
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

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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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