Structure of PDB 2q6b Chain A

Receptor sequence

>2q6bA (length=425) Species: 9606 (Homo sapiens)

HEPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYKLETLIETHE
RGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVG
VAGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMT
RGPVVRLPRACDSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIA
GRNLYIRFQSRSGDAMGMNMISKGTEKALSKLHEYFPEMQILAVSGNYCT
DKKPAAINWIEGRGKSVVCEAVIPAKVVREVLKTTTEAMIEVNINKNLVG
SAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTNE
DLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLA
RIVCGTVMAGELSLMAALAAGHLVK

3D structure

• PDB: 2q6b Design and synthesis of novel, conformationally restricted HMG-CoA reductase inhibitors.
• Chain: A
• Resolution: 2.0 Å

Enzymatic activity

• Catalytic site (original residue number in PDB): E559 K691 D767
• Catalytic site (residue number reindexed from 1): E120 K252 D328
• 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	HR2	A	R590 S661 V683 S684 D690 K692	R151 S222 V244 S245 D251 K253	MOAD: ic50=0.3nM PDBbind-CN: -logKd/Ki=9.52,IC50=0.3nM
BS02	HR2	A	E559 C561 L562 S565 R568 K735 A751 L853 L862	E120 C122 L123 S126 R129 K296 A312 L414 L423	MOAD: ic50=0.3nM PDBbind-CN: -logKd/Ki=9.52,IC50=0.3nM

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:2q6b, PDBe:2q6b, PDBj:2q6b
• PDBsum: 2q6b
• PubMed: 17574411
• UniProt: P04035|HMDH_HUMAN 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Gene Name=HMGCR)