5KDR

The crystal structure of carboxyltransferase from Staphylococcus Aureus bound to the antimicrobial agent moiramide B.

Summary for 5KDR

• Entry DOI: 10.2210/pdb5kdr/pdb
• Related: 2F9I
• Descriptor: Acetyl-coenzyme A carboxylase carboxyl transferase subunit alpha, Acetyl-coenzyme A carboxylase carboxyl transferase subunit beta, SULFATE ION, ... (7 entities in total)
• Functional Keywords: transferase, antibiotic, moiramide b, acetyl-coa carboxylase, carboxyltransferase, enolate
• Biological source: Staphylococcus aureus (strain USA300); More
• Cellular location: Cytoplasm : Q2FG38 Q2YTE0
• Total number of polymer chains: 2
• Total formula weight: 69470.73

Authors

Silvers, M.A.,Pakhomova, S.,Neau, D.,Silvers, W.C.,Anzalone, N.,Taylor, C.M.,Waldrop, G.L. (deposition date: 2016-06-08, release date: 2016-08-10, Last modification date: 2023-09-27)

Primary citation

Silvers, M.A.,Pakhomova, S.,Neau, D.B.,Silvers, W.C.,Anzalone, N.,Taylor, C.M.,Waldrop, G.L.
Crystal Structure of Carboxyltransferase from Staphylococcus aureus Bound to the Antibacterial Agent Moiramide B.
Biochemistry, 55:4666-4674, 2016

PubMed Abstract: The dramatic increase in the prevalence of antibiotic-resistant bacteria has necessitated a search for new antibacterial agents against novel targets. Moiramide B is a natural product, broad-spectrum antibiotic that inhibits the carboxyltransferase component of acetyl-CoA carboxylase, which catalyzes the first committed step in fatty acid synthesis. Herein, we report the 2.6 Å resolution crystal structure of moiramide B bound to carboxyltransferase. An unanticipated but significant finding was that moiramide B bound as the enol/enolate. Crystallographic studies demonstrate that the (4S)-methyl succinimide moiety interacts with the oxyanion holes of the enzyme, supporting the notion that an anionic enolate is the active form of the antibacterial agent. Structure-activity studies demonstrate that the unsaturated fatty acid tail of moiramide B is needed only for entry into the bacterial cell. These results will allow the design of new antibacterial agents against the bacterial form of carboxyltransferase.

PubMed: 27471863
DOI: 10.1021/acs.biochem.6b00641

Experimental method

X-RAY DIFFRACTION (2.6 Å)