Structure of PDB 1hwi Chain A

Receptor sequence

>1hwiA (length=393) Species: 9606 (Homo sapiens)

LSDAEIIQLVNLETLIETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNY
SLVMGACCENVIGYMPIPVGVAGPLCLDEKEFQVPMATTEGCLVASTNRG
CRAIGLGGGASSRVLADGMTRGPVVRLPRACDSAEVKAWLETSEGFAVIK
EAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMISKGTEKALS
KLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVRE
VLKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAA
QNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQ
MLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAGHL

3D structure

• PDB: 1hwi Structural mechanism for statin inhibition of HMG-CoA reductase.
• Chain: A
• Resolution: 2.3 Å

Enzymatic activity

• Catalytic site (original residue number in PDB): E559 K691 D767
• Catalytic site (residue number reindexed from 1): E90 K222 D298
• Enzyme Commision number: 1.1.1.34: hydroxymethylglutaryl-CoA reductase (NADPH).

Interaction with ligand

Site #	Ligand	Ligand chain	Binding residues on receptor (original residue number in PDB)	Binding residues on receptor (residue number reindexed from 1)	Binding affinity
BS01	115	A	R590 V683 S684 D690 K692	R121 V214 S215 D221 K223	MOAD: ic50=28nM BindingDB: IC50=28nM
BS02	ADP	A	A564 N567 R568 K722	A95 N98 R99 K253
BS03	115	A	E559 C561 L562 K735 A751 L853	E90 C92 L93 K266 A282 L384	MOAD: ic50=28nM BindingDB: IC50=28nM

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)