Structure of PDB 1hwk Chain D

Receptor sequence

>1hwkD (length=387) Species: 9606 (Homo sapiens)

SDAEIIQLETLIETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVM
GACCENVIGYMPIPVGVAGPLCLDEKEFQVPMATTEGCLVASTNRGCRAI
GLGGGASSRVLADGMTRGPVVRLPRACDSAEVKAWLETSEGFAVIKEAFD
STSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMISKGTEKALSKLHE
YFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREVLKT
TTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVG
SSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGV
QGACKDNPGENARQLARIVCGTVMAGELSLMAALAAG

3D structure

• PDB: 1hwk Structural mechanism for statin inhibition of HMG-CoA reductase.
• Chain: D
• Resolution: 2.22 Å

Enzymatic activity

• Catalytic site (original residue number in PDB): E559 K691 D767
• Catalytic site (residue number reindexed from 1): E86 K218 D294
• 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	117	D	E559 C561 L562 S565 R568 K735 A751 L853 A856 L857	E86 C88 L89 S92 R95 K262 A278 L380 A383 L384	MOAD: ic50=8nM BindingDB: IC50=6nM,Ki=6.2nM
BS02	ADP	D	F628 G652 D653 A654 G656 N658 M659 A826	F155 G179 D180 A181 G183 N185 M186 A353
BS03	117	D	R590 V683 S684 D690 K692	R117 V210 S211 D217 K219	MOAD: ic50=8nM BindingDB: IC50=6nM,Ki=6.2nM

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