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

被引：28
作者：
Hong, Seung Kon
Kim, Kook Han
Park, Joon Kyu
Jeong, Ki-Woong [2 ]
Kim, Yangmee [2 ]
Kim, Eunice EunKyeong [1 ]
机构：
[1] Korea Inst Sci & Technol, Biomed Res Ctr, Div Life Sci, Seoul 136791, South Korea
[2] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea
来源：
FEBS LETTERS | 2010年 / 584卷 / 06期
关键词：
Fatty-acid biosynthesis; FabD; MCAT; Antibacterial; Structure based drug design; FATTY-ACID BIOSYNTHESIS; STREPTOMYCES-COELICOLOR; CRYSTAL-STRUCTURE; ACP TRANSACYLASE; MCAT; TARGETS; SITE;
D O I：
10.1016/j.febslet.2010.02.038
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：1240 / 1244
页数：5
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