Structure of PDB 4p38 Chain A Binding Site BS02

Receptor Information
>4p38 Chain A (length=265) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EFRPEMLQGKKVIVTGASKGIGREMAYHLAKMGAHVVVTARSKETLQKVV
SHCLELGAASAHYIAGTMEDMTFAEQFVAQAGKLMGGLDMLILNHITNTS
LNLFHDDIHHVRKSMEVNFLSYVVLTVAALPMLKQSNGSIVVVSSLAGKV
AYPLVAAYSASKFALDGFFSSIRKEYSVSRVNVSITLCVLGLIDTETAMK
AVSGIVHMQAAPKEECALEIIKGGALRQEEVYYDSSRWTTLLIRNPSRKI
LEELYSTSYNWDRFI
Ligand information
Ligand ID21T
InChIInChI=1S/C25H31N3O3/c1-25(2,3)22-20(13-26-28(22)19-6-4-16(5-7-19)24(30)31)23(29)27-21-17-9-14-8-15(11-17)12-18(21)10-14/h4-7,13-15,17-18,21H,8-12H2,1-3H3,(H,27,29)(H,30,31)/t14-,15+,17-,18+,21-
InChIKeyXWBXJBSVYVJAMZ-RCQAVAAASA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.9.2CC(C)(C)c1c(cnn1c2ccc(cc2)C(=O)O)C(=O)NC3C4CC5CC(C4)CC3C5
CACTVS 3.385CC(C)(C)c1n(ncc1C(=O)NC2C3CC4CC(C3)CC2C4)c5ccc(cc5)C(O)=O
ACDLabs 12.01O=C(O)c1ccc(cc1)n2ncc(c2C(C)(C)C)C(=O)NC5C3CC4CC(C3)CC5C4
FormulaC25 H31 N3 O3
Name4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid
ChEMBL
DrugBank
ZINC
PDB chain4p38 Chain A Residue 302 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4p38 Novel acidic 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) inhibitor with reduced acyl glucuronide liability: the discovery of 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid (AZD8329).
Resolution2.8 Å
Binding residue
(original residue number in PDB)		S170 Y177 Y183 G216 L217 A223 A226
Binding residue
(residue number reindexed from 1)		S145 Y152 Y158 G191 L192 A198 A201
Annotation score1
Binding affinityBindingDB: IC50=9nM
Enzymatic activity
Catalytic site (original residue number in PDB) S170 Y183 K187
Catalytic site (residue number reindexed from 1) S145 Y158 K162
Enzyme Commision number 1.1.1.146: 11beta-hydroxysteroid dehydrogenase.
1.1.1.201: 7beta-hydroxysteroid dehydrogenase (NADP(+)).
Gene Ontology
Molecular Function
GO:0005496 steroid binding
GO:0016491 oxidoreductase activity
GO:0042803 protein homodimerization activity
GO:0047022 7-beta-hydroxysteroid dehydrogenase (NADP+) activity
GO:0050661 NADP binding
GO:0070524 11-beta-hydroxysteroid dehydrogenase (NADP+) activity
GO:0102196 cortisol dehydrogenase activity
Biological Process
GO:0006706 steroid catabolic process
GO:0008202 steroid metabolic process
GO:0030324 lung development
Cellular Component
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0016020 membrane
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:4p38, PDBe:4p38, PDBj:4p38
PDBsum4p38
PubMed23088558
UniProtP28845|DHI1_HUMAN 11-beta-hydroxysteroid dehydrogenase 1 (Gene Name=HSD11B1)

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