Structure of PDB 3s41 Chain A Binding Site BS02

Receptor Information
>3s41 Chain A (length=448) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
ENLYFQGMKKEKVEQILAEFQLQEEDLKKVMRRMQKEMDRGLRLETHEEA
SVKMLPTYVRSTPEGSEVGDFLSLDLGGTNFRVMLVKVGSVKTKHQMYSI
PEDAMTGTAEMLFDYISECISDFLDKHQMKHKKLPLGFTFSFPVRHEDID
KGILLNWTKGFKASGAEGNNVVGLLRDAIKRRGDFEMDVVAMVNDTVATM
ISCYYEDHQCEVGMIVGTGCNACYMEEMQNVELVEGDEGRMCVNTEWGAF
GDSGELDEFLLEYDRLVDESSANPGQQLYEKLIGGKYMGELVRLVLLRLV
DENLLFHGEASEQLRTRGAFETRFVSQVESDTGDRKQIYNILSTLGLRPS
TTDCDIVRRACESVSTRAAHMCSAGLAGVINRMRESRSEDVMRITVGVDG
SVYKLHPSFKERFHASVRRLTPSCEITFIESEEGSGRGAALVSAVACK
Ligand information
Ligand IDS41
InChIInChI=1S/C22H20N6O4/c1-12-8-24-19(11-23-12)27-21(29)14-6-17-16(5-13(2)31-17)18(7-14)32-15-9-25-20(26-10-15)22(30)28(3)4/h5-11H,1-4H3,(H,24,27,29)
InChIKeyMASKQITXHVYVFL-UHFFFAOYSA-N
SMILES
SoftwareSMILES
CACTVS 3.370CN(C)C(=O)c1ncc(Oc2cc(cc3oc(C)cc23)C(=O)Nc4cnc(C)cn4)cn1
ACDLabs 12.01O=C(N(C)C)c4ncc(Oc2cc(cc1oc(cc12)C)C(=O)Nc3ncc(nc3)C)cn4
OpenEye OEToolkits 1.7.2Cc1cc2c(o1)cc(cc2Oc3cnc(nc3)C(=O)N(C)C)C(=O)Nc4cnc(cn4)C
FormulaC22 H20 N6 O4
NameN,N-dimethyl-5-({2-methyl-6-[(5-methylpyrazin-2-yl)carbamoyl]-1-benzofuran-4-yl}oxy)pyrimidine-2-carboxamide
ChEMBLCHEMBL2165615
DrugBankDB15009
ZINCZINC000068246554
PDB chain3s41 Chain A Residue 4000 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB3s41 Designing glucokinase activators with reduced hypoglycemia risk: discovery of N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)-carbamoyl)benzofuran-4-yloxy)pyrimidine-2-carboxamide as a clinical candidate for the treatment of type 2 diabetes mellitus
Resolution2.18 Å
Binding residue
(original residue number in PDB)		R63 S69 I159 I211 Y214 Y215 M235 L451 V452 V455 A456
Binding residue
(residue number reindexed from 1)		R60 S66 I149 I201 Y204 Y205 M225 L441 V442 V445 A446
Annotation score1
Binding affinityBindingDB: EC50=190nM
Enzymatic activity
Catalytic site (original residue number in PDB) R85 S151 N166 D205
Catalytic site (residue number reindexed from 1) R82 S141 N156 D195
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:3s41, PDBe:3s41, PDBj:3s41
PDBsum3s41
PubMed
UniProtP35557|HXK4_HUMAN Hexokinase-4 (Gene Name=GCK)

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