Structure of PDB 2r4f Chain D Binding Site BS01

Receptor Information
>2r4f Chain D (length=394) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GAKFLSDAEIIQLVNETLIETHERGVSIRRQLLSKKLSEPSSLQYLPYRD
YNYSLVMGACCENVIGYMPIPVGVAGPLCLDEKEFQVPMATTEGCLVAST
NRGCRAIGLGGGASSRVLADGMTRGPVVRLPRACDSAEVKAWLETSEGFA
VIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMISKGTEK
ALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKV
VREVLKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQ
DAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQA
CLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAG
Ligand information
Ligand IDRIE
InChIInChI=1S/C29H36FN3O5/c1-18(2)27-25(15-14-23(34)16-24(35)17-26(36)37)33(22-12-10-21(30)11-13-22)31-28(27)29(38)32(4)19(3)20-8-6-5-7-9-20/h5-13,18-19,23-24,34-35H,14-17H2,1-4H3,(H,36,37)/t19-,23-,24-/m1/s1
InChIKeyMPDDTAJMJCESGV-CTUHWIOQSA-N
SMILES
SoftwareSMILES
ACDLabs 10.04O=C(O)CC(O)CC(O)CCc2c(c(nn2c1ccc(F)cc1)C(=O)N(C(c3ccccc3)C)C)C(C)C
OpenEye OEToolkits 1.5.0CC(C)c1c(n(nc1C(=O)N(C)[C@H](C)c2ccccc2)c3ccc(cc3)F)CC[C@H](C[C@H](CC(=O)O)O)O
CACTVS 3.341CC(C)c1c(CC[CH](O)C[CH](O)CC(O)=O)n(nc1C(=O)N(C)[CH](C)c2ccccc2)c3ccc(F)cc3
OpenEye OEToolkits 1.5.0CC(C)c1c(n(nc1C(=O)N(C)C(C)c2ccccc2)c3ccc(cc3)F)CCC(CC(CC(=O)O)O)O
CACTVS 3.341CC(C)c1c(CC[C@@H](O)C[C@@H](O)CC(O)=O)n(nc1C(=O)N(C)[C@H](C)c2ccccc2)c3ccc(F)cc3
FormulaC29 H36 F N3 O5
Name(3R,5R)-7-[1-(4-fluorophenyl)-4-(1-methylethyl)-3-{methyl[(1R)-1-phenylethyl]carbamoyl}-1H-pyrazol-5-yl]-3,5-dihydroxyheptanoic acid
ChEMBLCHEMBL1207355
DrugBank
ZINCZINC000014974373
PDB chain2r4f Chain C Residue 876 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB2r4f Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia.
Resolution1.7 Å
Binding residue
(original residue number in PDB)		E559 C561 L562 A564 S565 R568 K735 A751 L853 A856
Binding residue
(residue number reindexed from 1)		E93 C95 L96 A98 S99 R102 K269 A285 L387 A390
Annotation score1
Binding affinityMOAD: ic50=1.5nM
Enzymatic activity
Catalytic site (original residue number in PDB) E559 K691 D767
Catalytic site (residue number reindexed from 1) E93 K225 D301
Enzyme Commision number 1.1.1.34: hydroxymethylglutaryl-CoA reductase (NADPH).
Gene Ontology
Molecular Function
GO:0004420 hydroxymethylglutaryl-CoA reductase (NADPH) activity
GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
GO:0050661 NADP binding
Biological Process
GO:0008299 isoprenoid biosynthetic process
GO:0015936 coenzyme A metabolic process
Cellular Component
GO:0005789 endoplasmic reticulum membrane

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Biological Process
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Cellular Component
External links
PDB RCSB:2r4f, PDBe:2r4f, PDBj:2r4f
PDBsum2r4f
PubMed18072721
UniProtP04035|HMDH_HUMAN 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Gene Name=HMGCR)

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