Structure of PDB 3i4b Chain B Binding Site BS01

Receptor Information

>3i4b Chain B (length=347) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]

KVTTVVATPGQGPDRPQEVSYTDTKVIGNGSFGVVYQAKLCDSGELVAIK
KVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDEVYLNLVLDYV
PETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHRDIKPQ
NLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYT
SSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMN
PNYTEFKFPQIKAHPWTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEAC
AHSFFDELRDPNVKLPNGRDTPALFNFTTQELSSNPPLATILIPPHA

Ligand information

Ligand ID

Z48

InChI

InChI=1S/C24H23N5O2/c1-16-13-26-24(27-19-10-6-3-7-11-19)29-22(16)18-12-20(25-14-18)23(31)28-21(15-30)17-8-4-2-5-9-17/h2-14,21,25,30H,15H2,1H3,(H,28,31)(H,26,27,29)/t21-/m1/s1

InChIKey

PFHKAGAZRDERTK-OAQYLSRUSA-N

SMILES

Software	SMILES
ACDLabs 10.04	O=C(c3cc(c1nc(ncc1C)Nc2ccccc2)cn3)NC(c4ccccc4)CO
CACTVS 3.341	Cc1cnc(Nc2ccccc2)nc1c3c[nH]c(c3)C(=O)N[CH](CO)c4ccccc4
CACTVS 3.341	Cc1cnc(Nc2ccccc2)nc1c3c[nH]c(c3)C(=O)N[C@H](CO)c4ccccc4
OpenEye OEToolkits 1.5.0	Cc1cnc(nc1c2cc([nH]c2)C(=O)NC(CO)c3ccccc3)Nc4ccccc4
OpenEye OEToolkits 1.5.0	Cc1cnc(nc1c2cc([nH]c2)C(=O)N[C@H](CO)c3ccccc3)Nc4ccccc4

Formula

C24 H23 N5 O2

Name

N-[(1S)-2-hydroxy-1-phenylethyl]-4-[5-methyl-2-(phenylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide

PDB chain

3i4b Chain B Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]

Receptor-Ligand Complex Structure

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Structure summary

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PDB	3i4b Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control.
Resolution	2.3 Å
Binding residue (original residue number in PDB)	N64 G65 S66 G68 V70 A83 K85 Y134 V135 P136 L188 C199 D200
Binding residue (residue number reindexed from 1)	N29 G30 S31 G33 V35 A48 K50 Y99 V100 P101 L153 C164 D165
Annotation score	1
Binding affinity	MOAD: Ki=7nM PDBbind-CN: -logKd/Ki=8.15,Ki=7nM BindingDB: Ki=7nM

Enzymatic activity

Catalytic site (original residue number in PDB)	D181 K183 N186 D200 S219
Catalytic site (residue number reindexed from 1)	D146 K148 N151 D165 S184
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:3i4b, PDBe:3i4b, PDBj:3i4b
PDBsum	3i4b
PubMed	19827834
UniProt	P49841\|GSK3B_HUMAN Glycogen synthase kinase-3 beta (Gene Name=GSK3B)

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