Structure of PDB 4p38 Chain A Binding Site BS03

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 B Residue 302 [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]
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)		Y280 Y284
Binding residue
(residue number reindexed from 1)		Y255 Y259
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

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:4p38, PDBe:4p38, PDBj:4p38
PDBsum4p38
PubMed23088558
UniProtP28845|DHI1_HUMAN 11-beta-hydroxysteroid dehydrogenase 1 (Gene Name=HSD11B1)

[Back to BioLiP]