Structure of PDB 4pte Chain A Binding Site BS01

Receptor Information
>4pte Chain A (length=341) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KVTTVVATPGQGPDRPQEVSYTDTKVIGNGSFGVVYQAKLCDSGELVAIK
KVLQDFKNRELQIMRKLDHCNIVRLRYFFYSSDEVYLNLVLDYVPETVYR
VARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHRDIKPQNLLLDP
DTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVW
SAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEF
KFPQIKAHPWTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFD
ELRDPNVKLPNGRDTPALFNFTTQELSSNPPLATILIPPHA
Ligand information
Ligand ID2WF
InChIInChI=1S/C18H15N3O/c22-18(13-2-3-13)21-17-10-15(6-8-20-17)14-4-1-12-5-7-19-11-16(12)9-14/h1,4-11,13H,2-3H2,(H,20,21,22)
InChIKeyPGKFRHOTYGEBDX-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6c1cc(cc2c1ccnc2)c3ccnc(c3)NC(=O)C4CC4
CACTVS 3.385O=C(Nc1cc(ccn1)c2ccc3ccncc3c2)C4CC4
ACDLabs 12.01O=C(Nc1nccc(c1)c3cc2cnccc2cc3)C4CC4
FormulaC18 H15 N3 O
NameN-[4-(isoquinolin-7-yl)pyridin-2-yl]cyclopropanecarboxamide
ChEMBLCHEMBL3410100
DrugBank
ZINCZINC000230838457
PDB chain4pte 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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PDB4pte Discovery of new acylaminopyridines as GSK-3 inhibitors by a structure guided in-depth exploration of chemical space around a pyrrolopyridinone core.
Resolution2.033 Å
Binding residue
(original residue number in PDB)		F67 V70 A83 K85 Y134 V135 P136 R141 L188 D200
Binding residue
(residue number reindexed from 1)		F32 V35 A48 K50 Y93 V94 P95 R100 L147 D159
Annotation score1
Binding affinityMOAD: ic50=74nM
PDBbind-CN: -logKd/Ki=7.13,IC50=74nM
BindingDB: IC50=74nM
Enzymatic activity
Catalytic site (original residue number in PDB) D181 K183 N186 D200 S219
Catalytic site (residue number reindexed from 1) D140 K142 N145 D159 S178
Enzyme Commision number 2.7.11.1: non-specific serine/threonine protein kinase.
2.7.11.26: [tau protein] kinase.
Gene Ontology
Molecular Function
GO:0002020 protease binding
GO:0002039 p53 binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008013 beta-catenin binding
GO:0016301 kinase activity
GO:0019901 protein kinase binding
GO:0031625 ubiquitin protein ligase binding
GO:0034236 protein kinase A catalytic subunit binding
GO:0034452 dynactin binding
GO:0044024 histone H2AS1 kinase activity
GO:0048156 tau protein binding
GO:0050321 tau-protein kinase activity
GO:0051059 NF-kappaB binding
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
GO:0106310 protein serine kinase activity
Biological Process
GO:0001837 epithelial to mesenchymal transition
GO:0001954 positive regulation of cell-matrix adhesion
GO:0003170 heart valve development
GO:0005977 glycogen metabolic process
GO:0006338 chromatin remodeling
GO:0006468 protein phosphorylation
GO:0006983 ER overload response
GO:0007005 mitochondrion organization
GO:0007212 G protein-coupled dopamine receptor signaling pathway
GO:0007399 nervous system development
GO:0007623 circadian rhythm
GO:0008286 insulin receptor signaling pathway
GO:0009968 negative regulation of signal transduction
GO:0010508 positive regulation of autophagy
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0010719 negative regulation of epithelial to mesenchymal transition
GO:0010975 regulation of neuron projection development
GO:0016055 Wnt signaling pathway
GO:0016310 phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0019082 viral protein processing
GO:0021766 hippocampus development
GO:0030010 establishment of cell polarity
GO:0030011 maintenance of cell polarity
GO:0030154 cell differentiation
GO:0030336 negative regulation of cell migration
GO:0030516 regulation of axon extension
GO:0031175 neuron projection development
GO:0031333 negative regulation of protein-containing complex assembly
GO:0031334 positive regulation of protein-containing complex assembly
GO:0031398 positive regulation of protein ubiquitination
GO:0032007 negative regulation of TOR signaling
GO:0032092 positive regulation of protein binding
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032886 regulation of microtubule-based process
GO:0035556 intracellular signal transduction
GO:0036016 cellular response to interleukin-3
GO:0042752 regulation of circadian rhythm
GO:0043066 negative regulation of apoptotic process
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043547 positive regulation of GTPase activity
GO:0045597 positive regulation of cell differentiation
GO:0045668 negative regulation of osteoblast differentiation
GO:0045719 negative regulation of glycogen biosynthetic process
GO:0045724 positive regulation of cilium assembly
GO:0045732 positive regulation of protein catabolic process
GO:0046777 protein autophosphorylation
GO:0046825 regulation of protein export from nucleus
GO:0046827 positive regulation of protein export from nucleus
GO:0048511 rhythmic process
GO:0048814 regulation of dendrite morphogenesis
GO:0050770 regulation of axonogenesis
GO:0051093 negative regulation of developmental process
GO:0051128 regulation of cellular component organization
GO:0060070 canonical Wnt signaling pathway
GO:0060079 excitatory postsynaptic potential
GO:0070507 regulation of microtubule cytoskeleton organization
GO:0070885 negative regulation of calcineurin-NFAT signaling cascade
GO:0071109 superior temporal gyrus development
GO:0071300 cellular response to retinoic acid
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0099171 presynaptic modulation of chemical synaptic transmission
GO:0106027 neuron projection organization
GO:0150101 regulation of microtubule anchoring at centrosome
GO:1900034 regulation of cellular response to heat
GO:1900181 negative regulation of protein localization to nucleus
GO:1900271 regulation of long-term synaptic potentiation
GO:1901030 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
GO:1901984 negative regulation of protein acetylation
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:1903566 positive regulation of protein localization to cilium
GO:1904339 negative regulation of dopaminergic neuron differentiation
GO:1904646 cellular response to amyloid-beta
GO:1904781 positive regulation of protein localization to centrosome
GO:1904886 beta-catenin destruction complex disassembly
GO:2000077 negative regulation of type B pancreatic cell development
GO:2000466 negative regulation of glycogen (starch) synthase activity
GO:2000740 negative regulation of mesenchymal stem cell differentiation
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005813 centrosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0030424 axon
GO:0030425 dendrite
GO:0030877 beta-catenin destruction complex
GO:0098793 presynapse
GO:0098794 postsynapse
GO:0098978 glutamatergic synapse
GO:1990909 Wnt signalosome

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4pte, PDBe:4pte, PDBj:4pte
PDBsum4pte
PubMed25845281
UniProtP49841|GSK3B_HUMAN Glycogen synthase kinase-3 beta (Gene Name=GSK3B)

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