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Characterization and inhibitor discovery of one novel malonyl‐CoA: Acyl carrier protein transacylase (MCAT) from Helicobacter pylori
Author(s) -
Liu Weizhi,
Han Cong,
Hu Lihong,
Chen Kaixian,
Shen Xu,
Jiang Hualiang
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.085
Subject(s) - enzyme , circular dichroism , chemistry , biochemistry , helicobacter pylori , recombinant dna , genbank , non competitive inhibition , microbiology and biotechnology , biology , gene , genetics
Type II fatty acid synthesis (FAS II) is an essential process for bacteria survival, and malonyl‐CoA:acyl carrier protein transacylase (MCAT) is a key enzyme in FAS II pathway, which is responsible for transferring the malonyl group from malonyl‐CoA to the holo‐ACP by forming malonyl‐ACP. In this work, we described the cloning, characterization and enzymatic inhibition of a new MCAT from Helicobacter pylori strain SS1 ( Hp MCAT), and the gene sequence of Hpfab D was deposited in the GenBank database (Accession No. AY738332 ). Enzymatic characterization of Hp MCAT showed that the K m value for malonyl‐CoA was 21.01 ± 2.3 μM, and the thermal‐ and guanidinium hydrochloride‐induced unfolding processes for Hp MCAT were quantitatively investigated by circular dichroism spectral analyses. Moreover, a natural product, corytuberine, was discovered to demonstrate inhibitory activity against Hp MCAT with IC 50 value at 33.1 ± 3.29 μM. Further enzymatic assay results indicated that corytuberine inhibits Hp MCAT in an uncompetitive manner. To our knowledge, this is the firstly reported MCAT inhibitor to date. This current work is hoped to supply useful information for better understanding the MCAT features of H. pylori strain, and corytuberine might be used as a potential lead compound in the discovery of the antibacterial agents using Hp MCAT as target.