Structure of PDB 4h7c Chain A Binding Site BS02

Receptor Information
>4h7c Chain A (length=306) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
HQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHL
YNNEEQVGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLK
KAQLDYVDLYLIHSPMSLKPGEIFDIVDLCTTWEAMEKCKDAGLAKSIGV
SNFNRRQLEMILNKPGLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVA
YSALGSQRDKRWVDPNSPVLLEDPVLCALAKKHKRTPALIALRYQLQRGV
VVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLDRNLHYFNSDSFASHP
NYPYSD
Ligand information
Ligand ID10H
InChIInChI=1S/C16H20N2O3S/c1-13-5-2-3-12-18(13)22(20,21)15-9-7-14(8-10-15)17-11-4-6-16(17)19/h4,7-11,13H,2-3,5-6,12H2,1H3/t13-/m1/s1
InChIKeyMCVNUKURBWEELF-CYBMUJFWSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6C[C@@H]1CCCCN1S(=O)(=O)c2ccc(cc2)N3C=CCC3=O
ACDLabs 12.01O=S(=O)(c2ccc(N1C=CCC1=O)cc2)N3C(C)CCCC3
OpenEye OEToolkits 1.7.6CC1CCCCN1S(=O)(=O)c2ccc(cc2)N3C=CCC3=O
CACTVS 3.370C[C@@H]1CCCCN1[S](=O)(=O)c2ccc(cc2)N3C=CCC3=O
CACTVS 3.370C[CH]1CCCCN1[S](=O)(=O)c2ccc(cc2)N3C=CCC3=O
FormulaC16 H20 N2 O3 S
Name1-(4-{[(2R)-2-methylpiperidin-1-yl]sulfonyl}phenyl)-1,3-dihydro-2H-pyrrol-2-one
ChEMBL
DrugBank
ZINCZINC000103521245
PDB chain4h7c Chain A Residue 402 [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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PDB4h7c Synthesis and structure-activity relationships for 1-(4-(piperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-ones as novel non-carboxylate inhibitors of the aldo-keto reductase enzyme AKR1C3.
Resolution1.97 Å
Binding residue
(original residue number in PDB)		Y24 L54 S118 N167 W227 F306 F311
Binding residue
(residue number reindexed from 1)		Y20 L50 S114 N152 W212 F291 F296
Annotation score1
Binding affinityMOAD: ic50=0.088uM
Enzymatic activity
Catalytic site (original residue number in PDB) D50 Y55 K84 H117
Catalytic site (residue number reindexed from 1) D46 Y51 K80 H113
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:4h7c, PDBe:4h7c, PDBj:4h7c
PDBsum4h7c
PubMed23454516
UniProtP42330|AK1C3_HUMAN Aldo-keto reductase family 1 member C3 (Gene Name=AKR1C3)

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