1TVZ

Crystal structure of 3-hydroxy-3-methylglutaryl-coenzyme A synthase from Staphylococcus aureus

Summary for 1TVZ

• Entry DOI: 10.2210/pdb1tvz/pdb
• Related: 1TXT
• Descriptor: 3-hydroxy-3-methylglutaryl-CoA synthase, SULFATE ION (3 entities in total)
• Functional Keywords: hmg-coa synthase; hmgs, coenzyme a; thiolase fold; condensing enzyme; cholesterol biosynthesis, lyase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 1
• Total formula weight: 43422.47

Authors

Campobasso, N.,Patel, M.,Wilding, I.E.,Kallender, H.,Rosenberg, M.,Gwynn, M. (deposition date: 2004-06-30, release date: 2004-08-31, Last modification date: 2024-11-20)

Primary citation

Campobasso, N.,Patel, M.,Wilding, I.E.,Kallender, H.,Rosenberg, M.,Gwynn, M.
Staphylococcus aureus 3-hydroxy-3-methylglutaryl-CoA synthase: crystal structure and mechanism
J.Biol.Chem., 279:44883-44888, 2004

PubMed Abstract: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, a member of the family of acyl-condensing enzymes, catalyzes the first committed step in the mevalonate pathway and is a potential target for novel antibiotics and cholesterol-lowering agents. The Staphylococcus aureus mvaS gene product (43.2 kDa) was overexpressed in Escherichia coli, purified to homogeneity, and shown biochemically to be an HMG-CoA synthase. The crystal structure of the full-length enzyme was determined at 2.0-A resolution, representing the first structure of an HMG-CoA synthase from any organism. HMG-CoA synthase forms a homodimer. The monomer, however, contains an important core structure of two similar alpha/beta motifs, a fold that is completely conserved among acyl-condensing enzymes. This common fold provides a scaffold for a catalytic triad made up of Cys, His, and Asn required by these enzymes. In addition, a crystal structure of HMG-CoA synthase with acetoacetyl-CoA was determined at 2.5-A resolution. Together, these structures provide the structural basis for an understanding of the mechanism of HMG-CoA synthase.

PubMed: 15292254
DOI: 10.1074/jbc.M407882200

Experimental method

X-RAY DIFFRACTION (2 Å)