New design platform for malonyl-CoA-acyl carrier protein transacylase

作者：Hong Seung Kon; Kim Kook Han; Park Joon Kyu; Jeong Ki Woong; Kim Yangmee; Kim Eunice EunKyeong^*

来源：FEBS Letters, 2010, 584(6): 1240-1244.

DOI：10.1016/j.febslet.2010.02.038

• Fatty-acid biosynthesis
• FabD
• MCAT
• Antibacterial
• Structure based drug design

Malonyl-CoA-acyl carrier protein transacylase (MCAT) transfers the malonyl group from malonyl-CoA to holo-acyl carrier protein (ACP), and since malonyl-ACP is a key building block for fatty-acid biosynthesis it is considered as a promising antibacterial target. The crystal structures of MCAT from Staphylococcus aureus and Streptococcus pneumoniae have been determined at 1.46 and 2.1 angstrom resolution, respectively. In the SaMCAT structure, the N-terminal expression peptide of a neighboring molecule running in the opposite direction of malonyl-CoA makes extensive interactions with the highly conserved "Gly-Gln-Gly-Ser-Gln" stretch, suggesting a new design platform. Mutagenesis results suggest that Ser91 and His199 are the catalytic dyad.

• 出版日期2010-3-19