Structure of PDB 4yvv Chain A Binding Site BS02

Receptor Information
>4yvv Chain A (length=315) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
QCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLY
NNEEQVGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKK
AQLDYVDLYLIHSPMSLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCK
DAGLAKSIGVSNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNRSKLLDF
CKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPVLCALAKKHKRTPALI
ALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLDRNLHY
FNSDSFASHPNYPYS
Ligand information
Ligand IDGBM
InChIInChI=1S/C23H28ClN3O5S/c1-32-21-12-9-17(24)15-20(21)22(28)25-14-13-16-7-10-19(11-8-16)33(30,31)27-23(29)26-18-5-3-2-4-6-18/h7-12,15,18H,2-6,13-14H2,1H3,(H,25,28)(H2,26,27,29)
InChIKeyZNNLBTZKUZBEKO-UHFFFAOYSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01O=C(NC1CCCCC1)NS(=O)(=O)c3ccc(CCNC(=O)c2c(OC)ccc(Cl)c2)cc3
CACTVS 3.385COc1ccc(Cl)cc1C(=O)NCCc2ccc(cc2)[S](=O)(=O)NC(=O)NC3CCCCC3
OpenEye OEToolkits 1.9.2COc1ccc(cc1C(=O)NCCc2ccc(cc2)S(=O)(=O)NC(=O)NC3CCCCC3)Cl
FormulaC23 H28 Cl N3 O5 S
Name5-chloro-N-(2-{4-[(cyclohexylcarbamoyl)sulfamoyl]phenyl}ethyl)-2-methoxybenzamide;
Glibenclamide;
Glyburide
ChEMBLCHEMBL472
DrugBankDB01016
ZINCZINC000000537805
PDB chain4yvv Chain A Residue 402 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4yvv In vitro inhibition of AKR1Cs by sulphonylureas and the structural basis
Resolution2.3 Å
Binding residue
(original residue number in PDB)		Y24 L54 Y55 H117 W227 F306
Binding residue
(residue number reindexed from 1)		Y19 L49 Y50 H112 W222 F301
Annotation score1
Binding affinityMOAD: ic50=3.72uM
Enzymatic activity
Catalytic site (original residue number in PDB) D50 Y55 K84 H117
Catalytic site (residue number reindexed from 1) D45 Y50 K79 H112
Enzyme Commision number 1.1.1.-
1.1.1.188: prostaglandin-F synthase.
1.1.1.210: 3beta-(or 20alpha)-hydroxysteroid dehydrogenase.
1.1.1.239: 3alpha-(17beta)-hydroxysteroid dehydrogenase (NAD(+)).
1.1.1.357: 3alpha-hydroxysteroid 3-dehydrogenase.
1.1.1.53: 3alpha(or 20beta)-hydroxysteroid dehydrogenase.
1.1.1.62: 17beta-estradiol 17-dehydrogenase.
1.1.1.64: testosterone 17beta-dehydrogenase (NADP(+)).
Gene Ontology
Molecular Function
GO:0001758 retinal dehydrogenase activity
GO:0004032 aldose reductase (NADPH) activity
GO:0004033 aldo-keto reductase (NADPH) activity
GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity
GO:0004745 all-trans-retinol dehydrogenase (NAD+) activity
GO:0005515 protein binding
GO:0016491 oxidoreductase activity
GO:0016655 oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
GO:0032052 bile acid binding
GO:0036130 prostaglandin H2 endoperoxidase reductase activity
GO:0036131 prostaglandin D2 11-ketoreductase activity
GO:0045550 geranylgeranyl reductase activity
GO:0045703 ketoreductase activity
GO:0047017 prostaglandin F synthase activity
GO:0047020 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity
GO:0047023 androsterone dehydrogenase activity
GO:0047024 5alpha-androstane-3beta,17beta-diol dehydrogenase activity
GO:0047035 testosterone dehydrogenase (NAD+) activity
GO:0047044 androstan-3-alpha,17-beta-diol dehydrogenase activity
GO:0047045 testosterone 17-beta-dehydrogenase (NADP+) activity
GO:0047086 ketosteroid monooxygenase activity
GO:0047787 Delta4-3-oxosteroid 5beta-reductase activity
GO:0052650 all-trans-retinol dehydrogenase (NADP+) activity
Biological Process
GO:0001523 retinoid metabolic process
GO:0006629 lipid metabolic process
GO:0006693 prostaglandin metabolic process
GO:0007186 G protein-coupled receptor signaling pathway
GO:0007584 response to nutrient
GO:0008202 steroid metabolic process
GO:0008284 positive regulation of cell population proliferation
GO:0008584 male gonad development
GO:0009267 cellular response to starvation
GO:0016488 farnesol catabolic process
GO:0019371 cyclooxygenase pathway
GO:0030216 keratinocyte differentiation
GO:0042448 progesterone metabolic process
GO:0042572 retinol metabolic process
GO:0042574 retinal metabolic process
GO:0043170 macromolecule metabolic process
GO:0044597 daunorubicin metabolic process
GO:0044598 doxorubicin metabolic process
GO:0048385 regulation of retinoic acid receptor signaling pathway
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO:0061370 testosterone biosynthetic process
GO:0070293 renal absorption
GO:0071277 cellular response to calcium ion
GO:0071379 cellular response to prostaglandin stimulus
GO:0071384 cellular response to corticosteroid stimulus
GO:0071395 cellular response to jasmonic acid stimulus
GO:0071799 cellular response to prostaglandin D stimulus
GO:1900053 negative regulation of retinoic acid biosynthetic process
GO:2000224 regulation of testosterone biosynthetic process
GO:2000353 positive regulation of endothelial cell apoptotic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0070062 extracellular exosome

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4yvv, PDBe:4yvv, PDBj:4yvv
PDBsum4yvv
PubMed26362498
UniProtP42330|AK1C3_HUMAN Aldo-keto reductase family 1 member C3 (Gene Name=AKR1C3)

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