Structure of PDB 2gu8 Chain A Binding Site BS02

Receptor Information
>2gu8 Chain A (length=337) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SVKEFLAKAKEDFLKKWETPSQNTAQLDQFDRIKTLGTGSFGRVMLVKHK
ESGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDN
SNLYMVMEYVAGGEMFSHLRRIGRFSEPHARFYAAQIVLTFEYLHSLDLI
YRDLKPENLLIDEQGYIQVTDFGFAKRVKGRTWTLCGTPEYLAPEIILSK
GYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSS
DLKDLLRNLLQVDLTKRFGNLKNGVNDIKNHKWFATTDWIAIYQRKVEAP
FIPKFKGPGDTSNFDDYEEEEIRVSINEKCGKEFTEF
Ligand information
Ligand ID796
InChIInChI=1S/C19H19Cl2N5OS/c1-23-19-24-7-6-15(26-19)16-4-5-17(28-16)18(27)25-13(10-22)8-11-2-3-12(20)9-14(11)21/h2-7,9,13H,8,10,22H2,1H3,(H,25,27)(H,23,24,26)/t13-/m0/s1
InChIKeyHHOVRZGUSBMKKU-ZDUSSCGKSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.5.0CNc1nccc(n1)c2ccc(s2)C(=O)NC(Cc3ccc(cc3Cl)Cl)CN
CACTVS 3.341CNc1nccc(n1)c2sc(cc2)C(=O)N[C@H](CN)Cc3ccc(Cl)cc3Cl
OpenEye OEToolkits 1.5.0CNc1nccc(n1)c2ccc(s2)C(=O)N[C@@H](Cc3ccc(cc3Cl)Cl)CN
ACDLabs 10.04O=C(c2sc(c1nc(ncc1)NC)cc2)NC(Cc3ccc(Cl)cc3Cl)CN
CACTVS 3.341CNc1nccc(n1)c2sc(cc2)C(=O)N[CH](CN)Cc3ccc(Cl)cc3Cl
FormulaC19 H19 Cl2 N5 O S
NameN-[(1S)-2-AMINO-1-(2,4-DICHLOROBENZYL)ETHYL]-5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]THIOPHENE-2-CARBOXAMIDE;
NOVARTIS 273796
ChEMBLCHEMBL213618
DrugBankDB07235
ZINCZINC000016052084
PDB chain2gu8 Chain A Residue 1001 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
PDB2gu8 Discovery of 2-pyrimidyl-5-amidothiophenes as potent inhibitors for AKT: synthesis and SAR studies
Resolution2.2 Å
Binding residue
(original residue number in PDB)		L49 G50 T51 G52 G55 R56 A70 K72 E121 Y122 V123 N171 L173 T183 D184 F327
Binding residue
(residue number reindexed from 1)		L36 G37 T38 G39 G42 R43 A57 K59 E108 Y109 V110 N158 L160 T170 D171 F314
Annotation score1
Binding affinityMOAD: ic50=0.1nM
PDBbind-CN: -logKd/Ki=8.59,IC50=2.6nM
BindingDB: IC50=0.100000nM
Enzymatic activity
Catalytic site (original residue number in PDB) D166 K168 E170 N171 D184 T201
Catalytic site (residue number reindexed from 1) D153 K155 E157 N158 D171 T188
Enzyme Commision number 2.7.11.11: cAMP-dependent protein kinase.
Gene Ontology
Molecular Function
GO:0000287 magnesium ion binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004679 AMP-activated protein kinase activity
GO:0004691 cAMP-dependent protein kinase activity
GO:0004712 protein serine/threonine/tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0019901 protein kinase binding
GO:0019904 protein domain specific binding
GO:0030145 manganese ion binding
GO:0031625 ubiquitin protein ligase binding
GO:0034237 protein kinase A regulatory subunit binding
GO:0099103 channel activator activity
GO:0106310 protein serine kinase activity
Biological Process
GO:0001707 mesoderm formation
GO:0001843 neural tube closure
GO:0002027 regulation of heart rate
GO:0003091 renal water homeostasis
GO:0006397 mRNA processing
GO:0006468 protein phosphorylation
GO:0006611 protein export from nucleus
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
GO:0010737 protein kinase A signaling
GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
GO:0016241 regulation of macroautophagy
GO:0016310 phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0019221 cytokine-mediated signaling pathway
GO:0032024 positive regulation of insulin secretion
GO:0032703 negative regulation of interleukin-2 production
GO:0034380 high-density lipoprotein particle assembly
GO:0034605 cellular response to heat
GO:0035694 mitochondrial protein catabolic process
GO:0045542 positive regulation of cholesterol biosynthetic process
GO:0045667 regulation of osteoblast differentiation
GO:0045722 positive regulation of gluconeogenesis
GO:0045879 negative regulation of smoothened signaling pathway
GO:0046827 positive regulation of protein export from nucleus
GO:0048240 sperm capacitation
GO:0050804 modulation of chemical synaptic transmission
GO:0050850 positive regulation of calcium-mediated signaling
GO:0051726 regulation of cell cycle
GO:0055117 regulation of cardiac muscle contraction
GO:0061136 regulation of proteasomal protein catabolic process
GO:0070417 cellular response to cold
GO:0070613 regulation of protein processing
GO:0071333 cellular response to glucose stimulus
GO:0071374 cellular response to parathyroid hormone stimulus
GO:0071377 cellular response to glucagon stimulus
GO:0071872 cellular response to epinephrine stimulus
GO:0086064 cell communication by electrical coupling involved in cardiac conduction
GO:0099170 postsynaptic modulation of chemical synaptic transmission
GO:1903779 regulation of cardiac conduction
GO:1904262 negative regulation of TORC1 signaling
GO:1904539 negative regulation of glycolytic process through fructose-6-phosphate
GO:1990044 protein localization to lipid droplet
GO:2000810 regulation of bicellular tight junction assembly
Cellular Component
GO:0001669 acrosomal vesicle
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix
GO:0005813 centrosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005930 axoneme
GO:0005952 cAMP-dependent protein kinase complex
GO:0016607 nuclear speck
GO:0031410 cytoplasmic vesicle
GO:0031514 motile cilium
GO:0031594 neuromuscular junction
GO:0034704 calcium channel complex
GO:0036126 sperm flagellum
GO:0044853 plasma membrane raft
GO:0048471 perinuclear region of cytoplasm
GO:0070062 extracellular exosome
GO:0097546 ciliary base
GO:0098794 postsynapse
GO:0098978 glutamatergic synapse

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:2gu8, PDBe:2gu8, PDBj:2gu8
PDBsum2gu8
PubMed16765046
UniProtP17612|KAPCA_HUMAN cAMP-dependent protein kinase catalytic subunit alpha (Gene Name=PRKACA)

[Back to BioLiP]