Structure of PDB 5hex Chain A Binding Site BS01

Receptor Information
>5hex Chain A (length=880) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
DQVQKVDQYLYHMRLSDETLLEISKRFRKEMEKGLGATTHPTAAVKMLPT
FVRSTPDGTEHGEFLALDLGGTNFRVLWVKVTDNGLQKVEMENQIYAIPE
DISGTQLFDHIAECLANFMDKLQIKDKKLPLGFTFSFPCHQTKLDESFLV
GRDVVALIRKAIQRRGDFDIDIVAVVNDTVGTMMTCGYDDHNCEIGLIVG
TGSNACYMEEMRHIDMVEGDEGRMCINMEWGAFGDDGSLNDIRTEFDQEI
DMGSLNPGKQLFEKMISGMYMGELVRLILVKMAKEELLFGGKLSPELLNT
GRFETKDISDIEGEKDGIRKAREVLMRLGLDPTQEDCVATHRICQIVSTR
SASLCAATLAAVLQRIKENKGEERLRSTIGVDGSVYKKHPHFAKRLHKTV
RRLVPGCDVRFLRSEDGSGKGAAMVTAVAYRLADQHRARQKTLEHLQLSH
DQLLEVKRRMKVEMERGLSKETHASAPVKMLPTYVCATPDGTEKGDFLAL
DLGGTNFRVLLVRVRNGKWGGVEMHNKIYAIPQEVMHGTGDELFDHIVQC
IADFLEYMGMKGVSLPLGFTFSFPCQQNSLDESILLKWTKGFKASGCEGE
DVVTLLKEAIHRREEFDLDVVAVVNDTVGTMMTCGFEDPHCEVGLIVGTG
SNACYMEEMRNVELVEGEEGRMCVNMEWGAFGDNGCLDDFRTEFDVAVDE
LSLNPGKQRFEKMISGMYLGEIVRNILIDFTKRGLLFRGRISERLKTRGI
FETKFLSQIESDCLALLQVRAILQHLGLESTCDDSIIVKEVCTVVARRAA
QLCGAGMAAVVDRIRENRGLDALKVTVGVDGTLYKLHPHFAKVMHETVKD
LAPKCDVSFLQSEDGSGKGAALITAVACRI
Ligand information
Ligand ID604
InChIInChI=1S/C19H21BrN2O10S/c1-8-11(18(26)27)6-13(31-8)33(29,30)21-7-12-15(23)16(24)14(19(28)32-12)22-17(25)9-3-2-4-10(20)5-9/h2-6,12,14-16,19,21,23-24,28H,7H2,1H3,(H,22,25)(H,26,27)/t12-,14-,15-,16-,19+/m1/s1
InChIKeyGEVMYBPXLUPCSS-OREGDWJXSA-N
SMILES
SoftwareSMILES
CACTVS 3.385Cc1oc(cc1C(O)=O)[S](=O)(=O)NC[CH]2O[CH](O)[CH](NC(=O)c3cccc(Br)c3)[CH](O)[CH]2O
OpenEye OEToolkits 2.0.4Cc1c(cc(o1)S(=O)(=O)NC[C@@H]2[C@H]([C@@H]([C@H]([C@H](O2)O)NC(=O)c3cccc(c3)Br)O)O)C(=O)O
OpenEye OEToolkits 2.0.4Cc1c(cc(o1)S(=O)(=O)NCC2C(C(C(C(O2)O)NC(=O)c3cccc(c3)Br)O)O)C(=O)O
CACTVS 3.385Cc1oc(cc1C(O)=O)[S](=O)(=O)NC[C@H]2O[C@H](O)[C@H](NC(=O)c3cccc(Br)c3)[C@@H](O)[C@@H]2O
FormulaC19 H21 Br N2 O10 S
Name2-[(3-bromobenzene-1-carbonyl)amino]-6-{[(4-carboxy-5-methylfuran-2-yl)sulfonyl]amino}-2,6-dideoxy-alpha-D-glucopyranos e;
5-[[(2~{R},3~{S},4~{R},5~{R},6~{S})-5-[(3-bromophenyl)carbonylamino]-3,4,6-tris(oxidanyl)oxan-2-yl]methylsulfamoyl]-2-m ethyl-furan-3-carboxylic acid;
2-[(3-bromobenzene-1-carbonyl)amino]-6-{[(4-carboxy-5-methylfuran-2-yl)sulfonyl]amino}-2,6-dideoxy-alpha-D-glucose;
2-[(3-bromobenzene-1-carbonyl)amino]-6-{[(4-carboxy-5-methylfuran-2-yl)sulfonyl]amino}-2,6-dideoxy-D-glucose;
2-[(3-bromobenzene-1-carbonyl)amino]-6-{[(4-carboxy-5-methylfuran-2-yl)sulfonyl]amino}-2,6-dideoxy-glucose
ChEMBL
DrugBank
ZINCZINC000200849034
PDB chain5hex 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

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
PDB5hex Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors.
Resolution2.734 Å
Binding residue
(original residue number in PDB)		S155 P157 N208 D209 I229 G231 T232 G233 N235 E260 Q291 E294 G414 S415
Binding residue
(residue number reindexed from 1)		S136 P138 N177 D178 I198 G200 T201 G202 N204 E229 Q260 E263 G383 S384
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=8.00,IC50=0.010uM
Enzymatic activity
Catalytic site (original residue number in PDB) R539 S603 K618 D657
Catalytic site (residue number reindexed from 1) R508 S572 K587 D626
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

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:5hex, PDBe:5hex, PDBj:5hex
PDBsum5hex
PubMed26985301
UniProtP52789|HXK2_HUMAN Hexokinase-2 (Gene Name=HK2)

[Back to BioLiP]