Structure of PDB 1hwi Chain D

Receptor sequence

>1hwiD (length=374) Species: 9606 (Homo sapiens)

THERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPI
PVGVAGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLAD
GMTRGPVVRLPRACDSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHT
SIAGRNLYIRFQSRSGDAMGMNMISKGTEKALSKLHEYFPEMQILAVSGN
YCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREVLKTTTEAMIEVNINKN
LVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGP
TNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENAR
QLARIVCGTVMAGELSLMAALAAG

3D structure

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

Enzymatic activity

• Catalytic site (original residue number in PDB): E559 K691 D767
• Catalytic site (residue number reindexed from 1): E73 K205 D281
• 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	D	E559 C561 K735 A751 L853	E73 C75 K249 A265 L367	MOAD: ic50=28nM BindingDB: IC50=28nM
BS02	ADP	D	F628 G652 D653 A654 G656 N658 A826	F142 G166 D167 A168 G170 N172 A340
BS03	115	D	R590 V683 S684 D690 K691 K692	R104 V197 S198 D204 K205 K206	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)