1QAX

TERNARY COMPLEX OF PSEUDOMONAS MEVALONII HMG-COA REDUCTASE WITH HMG-COA AND NAD+

Summary for 1QAX

• Entry DOI: 10.2210/pdb1qax/pdb
• Descriptor: PROTEIN (3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE), 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: 4-electron oxido-reductase, oxidoreductase
• Biological source: Pseudomonas mevalonii
• Total number of polymer chains: 2
• Total formula weight: 92852.53

Authors

Tabernero, L.,Bochar, D.A.,Rodwell, V.W.,Stauffacher, C.V. (deposition date: 1999-04-06, release date: 1999-06-18, Last modification date: 2024-10-16)

Primary citation

Tabernero, L.,Bochar, D.A.,Rodwell, V.W.,Stauffacher, C.V.
Substrate-induced closure of the flap domain in the ternary complex structures provides insights into the mechanism of catalysis by 3-hydroxy-3-methylglutaryl-CoA reductase.
Proc.Natl.Acad.Sci.USA, 96:7167-7171, 1999

PubMed Abstract: 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase is the rate-limiting enzyme and the first committed step in the biosynthesis of cholesterol in mammals. We have determined the crystal structures of two nonproductive ternary complexes of HMG-CoA reductase, HMG-CoA/NAD+ and mevalonate/NADH, at 2.8 A resolution. In the structure of the Pseudomonas mevalonii apoenzyme, the last 50 residues of the C terminus (the flap domain), including the catalytic residue His381, were not visible. The structures of the ternary complexes reported here reveal a substrate-induced closing of the flap domain that completes the active site and aligns the catalytic histidine proximal to the thioester of HMG-CoA. The structures also present evidence that Lys267 is critically involved in catalysis and provide insights into the catalytic mechanism.

PubMed: 10377386
DOI: 10.1073/pnas.96.13.7167

Experimental method

X-RAY DIFFRACTION (2.8 Å)