Structure of PDB 1hwj Chain D

Receptor sequence

>1hwjD (length=392) Species: 9606 (Homo sapiens)

LSDAEIIQLVNALETLIETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYN
YSLVMGACCENVIGYMPIPVGVAGPLCLDEKEFQVPMATTEGCLVASTNR
GCRAIGLGGGASSRVLADGMTRGPVVRLPRACDSAEVKAWLETSEGFAVI
KEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMISKGTEKAL
SKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVR
EVLKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDA
AQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACL
QMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAG

3D structure

• PDB: 1hwj Structural mechanism for statin inhibition of HMG-CoA reductase.
• Chain: D
• Resolution: 2.26 Å

Enzymatic activity

• Catalytic site (original residue number in PDB): E559 K691 D767
• Catalytic site (residue number reindexed from 1): E91 K223 D299
• 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	ADP	D	A564 N567 R568 K722	A96 N99 R100 K254
BS02	116	D	E559 C561 L562 K735 A751 N755 L853	E91 C93 L94 K267 A283 N287 L385	MOAD: ic50=10nM
BS03	ADP	D	F628 G652 D653 A654 G656 M657 N658	F160 G184 D185 A186 G188 M189 N190
BS04	116	D	R590 V683 S684 D690 K691 K692	R122 V215 S216 D222 K223 K224	MOAD: ic50=10nM

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