Structure of PDB 1hwi Chain C Binding Site BS02

Receptor Information

>1hwi Chain C (length=374) Species: 9606 (Homo sapiens)

ERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPV
GVAGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGM
TRGPVVRLPRACDSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSI
AGRNLYIRFQSRSGDAMGMNMISKGTEKALSKLHEYFPEMQILAVSGNYC
TDKKPAAINWIEGRGKSVVCEAVIPAKVVREVLKTTTEAMIEVNINKNLV
GSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTN
EDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQL
ARIVCGTVMAGELSLMAALAAGHL

Ligand information

• Ligand ID: 115
• InChI: InChI=1S/C24H26FNO4/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30)/b12-11+/t18-,19-/m1/s1
• InChIKey: FJLGEFLZQAZZCD-MCBHFWOFSA-N
• SMILES:
  CACTVS 3.385: CC(C)n1c2ccccc2c(c3ccc(F)cc3)c1C=C[CH](O)C[CH](O)CC(O)=O
  OpenEye OEToolkits 1.7.6: CC(C)n1c2ccccc2c(c1/C=C/[C@H](C[C@H](CC(=O)O)O)O)c3ccc(cc3)F
  OpenEye OEToolkits 1.7.6: CC(C)n1c2ccccc2c(c1C=CC(CC(CC(=O)O)O)O)c3ccc(cc3)F
  CACTVS 3.385: CC(C)n1c2ccccc2c(c3ccc(F)cc3)c1/C=C/[C@@H](O)C[C@@H](O)CC(O)=O
  ACDLabs 12.01: c12ccccc1n(c(c2c3ccc(cc3)F)\C=C\C(CC(O)CC(=O)O)O)C(C)C
• Formula: C24 H26 F N O4
• Name: (3R,5S,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid;
  FLUVASTATIN
• ChEMBL: CHEMBL1078
• ZINC: ZINC000001886617
• PDB chain: 1hwi Chain D Residue 3

Receptor-Ligand Complex Structure

Structure summary

• PDB: 1hwi Structural mechanism for statin inhibition of HMG-CoA reductase.
• Resolution: 2.3 Å
• Binding residue (original residue number in PDB): E559 C561 L562 K735 A751 L853
• Binding residue (residue number reindexed from 1): E71 C73 L74 K247 A263 L365
• Annotation score: 1
• Binding affinity: MOAD: ic50=28nM
  BindingDB: IC50=28nM

Enzymatic activity

• Catalytic site (original residue number in PDB): E559 K691 D767
• Catalytic site (residue number reindexed from 1): E71 K203 D279
• 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

External links

• PDB: RCSB:1hwi, PDBe:1hwi, PDBj:1hwi
• PDBsum: 1hwi
• PubMed: 11349148
• UniProt: P04035|HMDH_HUMAN 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Gene Name=HMGCR)