Malonyl-CoA: acyl carrier protein transacylase from Helicobacter pylori: Crystal structure and its interaction with acyl carrier protein
Malonyl-CoA: acyl carrier protein transacylase (MCAT) is a critical enzyme responsible for the transfer of the malonyl moiety to holo-acyl carrier protein (ACP) forming the malonyl-ACP intermediates in the initiation step of type Ⅱfatty acid synthesis (FAS Ⅱ) in bacteria. MCAT has been considered as an attractive drug target in the discovery of antibacterial agents. In this study, the crystal structure of MCAT from Helicobacter pylori (Hp) at 2.5 (A) resolution is reported, and the interaction of HpMCAT with HpACP is extensively investigated by using computational docking, GST-pull-down, and surface plasmon resonance (SPR) technology-based assays. The crystal structure results reveal that HpMCAT has a compact folding composed of a large subdomain with a similar core as in α/β hydrolases, and a similar ferredoxin-like small subdomain as in acylphosphatases. The docking result suggests two positively charged areas near the entrance of the active site of HpMCAT as the ACP-binding region. Binding assay research shows that HpMCAT demonstrates a moderately binding ability against HpACP. The solved 3D structure of HpMCAT is expected to supply useful information tbr the structure-based discovery of novel inhibitors against MCAT, and the quantitative study of HpMCAT interaction with HpACP is hoped to give helpful hints in the understanding of the detailed catalytic mechanisms for HpMCAT.
Helicobacter pylori Manoyl-CoA: acyl carrier protein transacylase (MCAT) acyl carrier protein (ACP) fatty acid biosynthesis crystal structure
LIANG ZHANG WEIZHI LIU JIANFENG XIAO TIANCEN HU JING CHEN KAIXIAN CHEN HUALIANG JIANG XU SHEN
Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica,Chinese Academy of Sciences, Shanghai 201203, China
国际会议
广州
英文
13-21
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）