Structural highlights
Function
[ACCA_STAA3] Component of the acetyl coenzyme A carboxylase (ACC) complex. First, biotin carboxylase catalyzes the carboxylation of biotin on its carrier protein (BCCP) and then the CO(2) group is transferred by the carboxyltransferase to acetyl-CoA to form malonyl-CoA.[HAMAP-Rule:MF_00823] [ACCD_STAAB] Component of the acetyl coenzyme A carboxylase (ACC) complex. Biotin carboxylase (BC) catalyzes the carboxylation of biotin on its carrier protein (BCCP) and then the CO(2) group is transferred by the transcarboxylase to acetyl-CoA to form malonyl-CoA.
Publication Abstract from PubMed
The dramatic increase in 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 A 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 only needed for entry into the bacterial cell. These results will enable the design of new antibacterial agents against the bacterial form of carboxyltransferase.
The Crystal Structure of Carboxyltransferase from Staphylococcus aureus Bound to the Antibacterial Agent Moiramide B.,Silvers MA, Pakhomova S, Neau DB, Silvers WC, Anzalone N, Taylor CM, Waldrop GL Biochemistry. 2016 Jul 29. PMID:27471863[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Silvers MA, Pakhomova S, Neau DB, Silvers WC, Anzalone N, Taylor CM, Waldrop GL. The Crystal Structure of Carboxyltransferase from Staphylococcus aureus Bound to the Antibacterial Agent Moiramide B. Biochemistry. 2016 Jul 29. PMID:27471863 doi:http://dx.doi.org/10.1021/acs.biochem.6b00641
