Structure of PDB 1hw8 Chain A

Receptor sequence

>1hw8A (length=404) Species: 9606 (Homo sapiens)

EPRPNEECLSDAEIIQLVNPAYKLETLIETHERGVSIRRQLLSKKLSEPS
SLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDEKEFQVPMAT
TEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRACDSAEVKA
WLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGM
NMISKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVV
CEAVIPAKVVREVLKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIV
TAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGG
GTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAAL
AAGH

3D structure

• PDB: 1hw8 Structural mechanism for statin inhibition of HMG-CoA reductase.
• Chain: A
• Resolution: 2.1 Å

Enzymatic activity

• Catalytic site (original residue number in PDB): E559 K691 D767
• Catalytic site (residue number reindexed from 1): E102 K234 D310
• 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	114	A	R590 S684 D690 K692	R133 S227 D233 K235	MOAD: ic50=23nM
BS02	114	A	E559 S565 K735 A751 N755 L853	E102 S108 K278 A294 N298 L396	MOAD: ic50=23nM
BS03	ADP	A	Y479 N529	Y22 N72

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:1hw8, PDBe:1hw8, PDBj:1hw8
• PDBsum: 1hw8
• PubMed: 11349148
• UniProt: P04035|HMDH_HUMAN 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Gene Name=HMGCR)