Structure of PDB 5hg1 Chain A Binding Site BS01

Receptor Information
>5hg1 Chain A (length=867) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
DQVQKVDQYLYHMRLSDETLLEISKRFRKEMEKGLGATTHPTAAVKMLPT
FVRSTPDGTEHGEFLALDLGGTNFRVLWVKVTDNGLQKVEMENQIYGTQL
FDHIAECLANFMDKLQIKDKKLPLGFTFSFPCHQTKLDESFLVSGRDVVA
LIRKAIQIDIVAVVNDTVGTMMTCGYDDHNCEIGLIVGTGSNACYMEEMR
HIDMVEGDEGRMCINMEWGAFGDDGSLNDIRTEFDQEIDMGSLNPGKQLF
EKMISGMYMGELVRLILVKMAKEELLFGGKLSPELLNTGRFETKDISDIE
GEKDGIRKAREVLMRLGLDPTQEDCVATHRICQIVSTRSASLCAATLAAV
LQRIKENKGEERLRSTIGVDGSVYKKHPHFAKRLHKTVRRLVPGCDVRFL
RSEDGSGKGAAMVTAVAYRLADQHRARQKTLEHLQLSHDQLLEVKRRMKV
EMERGLSKETHASAPVKMLPTYVCATPDGTEKGDFLALDLGGTNFRVLLV
RVRNGGVEMHNKIYAIPQEVMHGTGDELFDHIVQCIADFLEYMGMKGVSL
PLGFTFSFPCQQNSLDESILLKWTKGFKASGCEGEDVVTLLKEAIHRREE
FDLDVVAVVNDTVGTMMTCGFEDPHCEVGLIVGTGSNACYMEEMRNVELV
EGEEGRMCVNMEWGAFGDNGCLDDFRTEFDVAVDELSLNPGKQRFEKMIS
GMYLGEIVRNILIDFTKRGLLFRGRISERLKTRGIFETKFLSQIESDCLA
LLQVRAILQHLGLESTCDDSIIVKEVCTVVARRAAQLCGAGMAAVVDRIR
ENRGLDALKVTVGVDGTLYKLHPHFAKVMHETVKDLAPKCDVSFLQSEDG
SGKGAALITAVACRIRE
Ligand information
Ligand ID62C
InChIInChI=1S/C15H17Cl2NO6/c16-8-3-1-7(5-9(8)17)2-4-11(20)18-12-14(22)13(21)10(6-19)24-15(12)23/h1-5,10,12-15,19,21-23H,6H2,(H,18,20)/b4-2+/t10-,12-,13-,14-,15+/m1/s1
InChIKeyZBHWRKZTEDNOAJ-GJAUZLMESA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.4c1cc(c(cc1/C=C/C(=O)N[C@@H]2[C@H]([C@@H]([C@H](O[C@@H]2O)CO)O)O)Cl)Cl
CACTVS 3.385OC[CH]1O[CH](O)[CH](NC(=O)C=Cc2ccc(Cl)c(Cl)c2)[CH](O)[CH]1O
OpenEye OEToolkits 2.0.4c1cc(c(cc1C=CC(=O)NC2C(C(C(OC2O)CO)O)O)Cl)Cl
ACDLabs 12.01C2(C(CO)OC(C(NC(=O)\C=C\c1ccc(c(c1)Cl)Cl)C2O)O)O
CACTVS 3.385OC[C@H]1O[C@H](O)[C@H](NC(=O)\C=C\c2ccc(Cl)c(Cl)c2)[C@@H](O)[C@@H]1O
FormulaC15 H17 Cl2 N O6
Name2-deoxy-2-{[(2E)-3-(3,4-dichlorophenyl)prop-2-enoyl]amino}-alpha-D-glucopyranose
ChEMBL
DrugBank
ZINCZINC000205324579
PDB chain5hg1 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

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PDB5hg1 Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors.
Resolution2.76 Å
Binding residue
(original residue number in PDB)		P605 K618 T620 K621 N656 D657 I677 G681 N683 E708 N735 K738 Q739 E742
Binding residue
(residue number reindexed from 1)		P559 K572 T574 K575 N610 D611 I631 G635 N637 E662 N689 K692 Q693 E696
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=5.20,IC50=6.3uM
Enzymatic activity
Catalytic site (original residue number in PDB) R539 S603 K618 D657
Catalytic site (residue number reindexed from 1) R496 S557 K572 D611
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
Biological Process
GO:0001666 response to hypoxia
GO:0001678 intracellular glucose homeostasis
GO:0002931 response to ischemia
GO:0005975 carbohydrate metabolic process
GO:0006002 fructose 6-phosphate metabolic process
GO:0006006 glucose metabolic process
GO:0006096 glycolytic process
GO:0007595 lactation
GO:0008637 apoptotic mitochondrial changes
GO:0016310 phosphorylation
GO:0019318 hexose metabolic process
GO:0035795 negative regulation of mitochondrial membrane permeability
GO:0045766 positive regulation of angiogenesis
GO:0046324 regulation of D-glucose import
GO:0046835 carbohydrate phosphorylation
GO:0051156 glucose 6-phosphate metabolic process
GO:0061621 canonical glycolysis
GO:0072655 establishment of protein localization to mitochondrion
GO:0072656 maintenance of protein location in mitochondrion
GO:1901135 carbohydrate derivative metabolic process
GO:1990830 cellular response to leukemia inhibitory factor
GO:2000378 negative regulation of reactive oxygen species metabolic process
Cellular Component
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005813 centrosome
GO:0005829 cytosol
GO:0016020 membrane
GO:0016529 sarcoplasmic reticulum
GO:0043231 intracellular membrane-bounded organelle

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:5hg1, PDBe:5hg1, PDBj:5hg1
PDBsum5hg1
PubMed26985301
UniProtP52789|HXK2_HUMAN Hexokinase-2 (Gene Name=HK2)

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