Structure of PDB 4isg Chain A Binding Site BS02

Receptor Information

>4isg Chain A (length=418) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]

KPMPLTLVEQILAEFQLQEEDLKKVMRRMQKEMDRGLRLETHEEASVKML
PTYVRSTPEGSEVGDFLSLDLGGTNFRVMLVKVGEQWSVKTKHQMYSIPE
DAMTGTAEMLFDYISECISDFLDKHQMKHKKLPLGFTFNVVGLLRDAIKR
RGDFEMDVVAMVNDTVATMISCYYEDHQCEVGMIVGTGCNACYMEEMQNV
ELVEGDEGRMCVNTEWGAFGDSGELDEFLLEYDRLVDESSANPGQQLYEK
LIGGKYMGELVRLVLLRLVDENLLFHGEASEQLRTRGAFETRFVSQVESD
TGDRKQIYNILSTLGLRPSTTDCDIVRRACESVSTRAAHMCSAGLAGVIN
RMRESRMRITVGVDGSVYKLHPSFKERFHASVRRLTPSCEITFIESESGR
GAALVSAVACKKACMLGQ

Ligand information

Ligand ID

1FY

InChI

InChI=1S/C17H26N4O4S2/c1-27(24,25)20-8-9-21(15(22)12-20)14(11-13-5-3-2-4-6-13)16(23)19-17-18-7-10-26-17/h7,10,13-14H,2-6,8-9,11-12H2,1H3,(H,18,19,23)/t14-/m0/s1

InChIKey

MCVZXAIMSDHSPP-AWEZNQCLSA-N

SMILES

Software	SMILES
CACTVS 3.370	C[S](=O)(=O)N1CCN([C@@H](CC2CCCCC2)C(=O)Nc3sccn3)C(=O)C1
OpenEye OEToolkits 1.7.6	CS(=O)(=O)N1CCN(C(=O)C1)[C@@H](CC2CCCCC2)C(=O)Nc3nccs3
ACDLabs 12.01	O=C(Nc1nccs1)C(N2C(=O)CN(S(=O)(=O)C)CC2)CC3CCCCC3
CACTVS 3.370	C[S](=O)(=O)N1CCN([CH](CC2CCCCC2)C(=O)Nc3sccn3)C(=O)C1
OpenEye OEToolkits 1.7.6	CS(=O)(=O)N1CCN(C(=O)C1)C(CC2CCCCC2)C(=O)Nc3nccs3

Formula

C17 H26 N4 O4 S2

Name

(2S)-3-cyclohexyl-2-[4-(methylsulfonyl)-2-oxopiperazin-1-yl]-N-(1,3-thiazol-2-yl)propanamide

PDB chain

4isg Chain A 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	4isg Design, synthesis and SAR of novel glucokinase activators.
Resolution	2.645 Å
Binding residue (original residue number in PDB)	Y61 V62 R63 S64 E67 W99 Y214 K458 K459
Binding residue (residue number reindexed from 1)	Y53 V54 R55 S56 E59 W87 Y173 K411 K412
Annotation score	1
Binding affinity	BindingDB: EC50=1600nM

Enzymatic activity

Catalytic site (original residue number in PDB)	R85 D205
Catalytic site (residue number reindexed from 1)	R77 D164
Enzyme Commision number	2.7.1.1: hexokinase.

Gene Ontology

	Molecular Function
GO:0004340	glucokinase activity
GO:0004396	hexokinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0005536	D-glucose binding
GO:0008865	fructokinase activity
GO:0016301	kinase activity
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0019158	mannokinase activity
GO:0141089	glucose sensor activity

	Biological Process
GO:0001678	intracellular glucose homeostasis
GO:0005975	carbohydrate metabolic process
GO:0006006	glucose metabolic process
GO:0006007	glucose catabolic process
GO:0006096	glycolytic process
GO:0006110	regulation of glycolytic process
GO:0006739	NADP metabolic process
GO:0009749	response to glucose
GO:0016310	phosphorylation
GO:0019318	hexose metabolic process
GO:0032024	positive regulation of insulin secretion
GO:0032869	cellular response to insulin stimulus
GO:0042593	glucose homeostasis
GO:0043266	regulation of potassium ion transport
GO:0044320	cellular response to leptin stimulus
GO:0045721	negative regulation of gluconeogenesis
GO:0045725	positive regulation of glycogen biosynthetic process
GO:0046835	carbohydrate phosphorylation
GO:0050796	regulation of insulin secretion
GO:0051156	glucose 6-phosphate metabolic process
GO:0061621	canonical glycolysis
GO:0070509	calcium ion import
GO:1901135	carbohydrate derivative metabolic process

	Cellular Component
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005829	cytosol

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Molecular Function

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Biological Process

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Cellular Component

External links

PDB	RCSB:4isg, PDBe:4isg, PDBj:4isg
PDBsum	4isg
PubMed	23434031
UniProt	P35557\|HXK4_HUMAN Hexokinase-4 (Gene Name=GCK)

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