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Malonyl‐CoA: acyl carrier protein transacylase from Helicobacter pylori : Crystal structure and its interaction with acyl carrier protein
Author(s) -
Zhang Liang,
Liu Weizhi,
Xiao Jianfeng,
Hu Tiancen,
Chen Jing,
Chen Kaixian,
Jiang Hualiang,
Shen Xu
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.072757307
Subject(s) - acyl carrier protein , docking (animal) , chemistry , surface plasmon resonance , moiety , active site , hydrolase , crystal structure , binding site , enzyme , stereochemistry , biochemistry , crystallography , biosynthesis , nanotechnology , nanoparticle , materials science , medicine , nursing
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 II fatty 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 Å resolution is reported, and the interaction of Hp MCAT with Hp ACP is extensively investigated by using computational docking, GST‐pull‐down, and surface plasmon resonance (SPR) technology‐based assays. The crystal structure results reveal that Hp MCAT 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 Hp MCAT as the ACP‐binding region. Binding assay research shows that Hp MCAT demonstrates a moderately binding ability against Hp ACP. The solved 3D structure of Hp MCAT is expected to supply useful information for the structure‐based discovery of novel inhibitors against MCAT, and the quantitative study of Hp MCAT interaction with Hp ACP is hoped to give helpful hints in the understanding of the detailed catalytic mechanisms for Hp MCAT.