Structure of PDB 2r4f Chain C Binding Site BS01

Receptor Information
>2r4f Chain C (length=404) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
PNEECLQILGNGAKFLSDAEIIQLVETLIETHERGVSIRRQLLSKKLSEP
SSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDEKEFQVPMA
TTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRACDSAEVK
AWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMG
MNMISKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSV
VCEAVIPAKVVREVLKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANI
VTAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVG
GGTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAA
LAAG
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)		R590 S661 V683 S684 D690 K692
Binding residue
(residue number reindexed from 1)		R134 S205 V227 S228 D234 K236
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) E103 K235 D311
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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Molecular Function
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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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