Structure of PDB 4hx5 Chain A Binding Site BS01

Receptor Information
>4hx5 Chain A (length=261) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EEFRPEMLQGKKVIVTGASKGIGREMAYHLAKMGAHVVVTARSKETLQKV
VSHCLELGAASAHYIAGTMEDMTFAEQFVAQAGKLMGGLDMLILNHITNT
SLNLFHDDIHHVRKSMEVNFLSYVVLTVAALPMLKQSNGSIVVVSSLAGK
VAYPMVAAYSASKFALDGFFSSIRKEYSVSRVNVSITLCVLGLIDTETAM
KAVSGIVHMQAAPKEECALEIIKGGALRQEEVYYDSSLWTTLLIRNPSRK
ILEFLYSTSYN
Ligand information
Ligand ID19V
InChIInChI=1S/C33H45N7O2/c1-32(2,3)38-12-10-37(11-13-38)25-8-9-28(35-21-25)39-14-15-40(27-7-5-4-6-26(27)39)31(42)36-29-23-16-22-17-24(29)20-33(18-22,19-23)30(34)41/h4-9,21-24,29H,10-20H2,1-3H3,(H2,34,41)(H,36,42)/t22-,23-,24+,29-,33-
InChIKeyRZUKTDWPBQOSBE-PKZLOJIYSA-N
SMILES
SoftwareSMILES
CACTVS 3.370CC(C)(C)N1CCN(CC1)c2ccc(nc2)N3CCN(C(=O)NC4[CH]5CC6C[CH]4CC(C6)(C5)C(N)=O)c7ccccc37
OpenEye OEToolkits 1.7.6CC(C)(C)N1CCN(CC1)c2ccc(nc2)N3CCN(c4c3cccc4)C(=O)NC5[C@@H]6CC7C[C@H]5CC(C6)(C7)C(=O)N
OpenEye OEToolkits 1.7.6CC(C)(C)N1CCN(CC1)c2ccc(nc2)N3CCN(c4c3cccc4)C(=O)NC5C6CC7CC5CC(C7)(C6)C(=O)N
ACDLabs 12.01O=C(N)C71CC6CC(C1)C(NC(=O)N5c2ccccc2N(c4ncc(N3CCN(C(C)(C)C)CC3)cc4)CC5)C(C6)C7
CACTVS 3.370CC(C)(C)N1CCN(CC1)c2ccc(nc2)N3CCN(C(=O)NC4[C@H]5CC6C[C@@H]4CC(C6)(C5)C(N)=O)c7ccccc37
FormulaC33 H45 N7 O2
Name4-[5-(4-tert-butylpiperazin-1-yl)pyridin-2-yl]-N-[(1R,2S,3S,5S,7s)-5-carbamoyltricyclo[3.3.1.1~3,7~]dec-2-yl]-3,4-dihydroquinoxaline-1(2H)-carboxamide
ChEMBL
DrugBank
ZINC
PDB chain4hx5 Chain A Residue 301 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4hx5 Discovery of SAR184841, a potent and long-lasting inhibitor of 11beta-hydroxysteroid dehydrogenase type 1, active in a physiopathological animal model of T2D
Resolution2.19 Å
Binding residue
(original residue number in PDB)		I121 S170 L171 Y177 Y183 G216 L217 T222 A226 M233 S261 T264
Binding residue
(residue number reindexed from 1)		I97 S146 L147 Y153 Y159 G192 L193 T198 A202 M209 S237 T240
Annotation score1
Binding affinityMOAD: ic50=4nM
Enzymatic activity
Catalytic site (original residue number in PDB) S170 Y183 K187
Catalytic site (residue number reindexed from 1) S146 Y159 K163
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:4hx5, PDBe:4hx5, PDBj:4hx5
PDBsum4hx5
PubMed23478147
UniProtP28845|DHI1_HUMAN 11-beta-hydroxysteroid dehydrogenase 1 (Gene Name=HSD11B1)

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