期刊
BIOCHEMICAL JOURNAL
卷 418, 期 -, 页码 369-378出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20082011
关键词
arylamine N-acetyltransferase (NAT); cholesterol; heat stability; 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid hydrolase (HsaD); Mycobacterium tuberculosis; survival
资金
- Wellcome Trust
- Natural Science and Engineering Council of Canada
- Linacre College, Oxford, U.K.
- Cancer Research UK [6947] Funding Source: researchfish
In Mycobacterium tuberculosis, the genes hsaD (2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid hydrolase) and nat (arylamine N-acetyltransferase) are essential for survival inside of host macrophages. These genes act Lis an operon and have been Suggested to he involved in cholesterol metabolism. However, the role of NAT in this catabolic pathway has not been determined. In in effort to better understand the function of these proteins, we have expressed, purified and characterized TBNAT (NAT from M. tuberculosis) and HsaD (2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid hydrolase) from M. tuberculosis. Both proteins demonstrated remarkable heat stability with TBNAT and HsaD retaining > 95 % of their activity after incubation at 60 degrees C for 30 min. The first and second domains of TBNAT were demonstrated to be very important to the heat stability of the protein, as the transfer of these domains caused a dramatic reduction in the heat stability. The specific activity of TBNAT was tested against a broad range of acyl-CoA cofactors using hydralazine as a substrate. TBNAT was found to be able to utilize not just acetylCoA, but also n-propionyl-CoA and acetoacetyl-CoA, although at a lower rate. As propionyl-CoA is a product of cholesterol catabolism, we propose that NAT Could have a role in the Utilization of this important cofactor.
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