Biochemical, structural, and functional studies reveal that MAB_4324c from Mycobacterium abscessus is an active tandem repeat N -acetyltransferase

FEBS Letters

article

Husam M. A. B. Alsarraf¹  Kien Lam Ung¹  Matt D. Johansen¹  Juliette Dimon¹  Vincent Olieric³  Laurent Kremer¹  Mickaël Blaise¹ 

[1] IRIM, CNRS, Université de Montpellier;Department of Molecular Biology and Genetics, Aarhus University;Swiss Light Source, Paul Scherrer Institute;INSERM

关键词: GCN5;    infection;    intracellular survival;    macrophage;    Mycobacterium abscessus;    N-acetyltransferase;    X-ray structure;   

DOI  :  10.1002/1873-3468.14360

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mycobacterium abscessus is a pathogenic non-tuberculous mycobacterium that possesses an intrinsic drug resistance profile. Several N -acetyltransferases mediate drug resistance and/or participate in M. abscessus virulence. Mining the M. abscessus genome has revealed genes encoding additional N -acetyltransferases whose functions remain uncharacterized, among them MAB_4324c. Here, we showed that the purified MAB_4324c protein is a N -acetyltransferase able to acetylate small polyamine substrates. The crystal structure of MAB_4324c was solved at high resolution in complex with its cofactor, revealing the presence of two GCN5-related N -acetyltransferase domains and a cryptic binding site for NADPH. Genetic studies demonstrate that MAB_4324c is not essential for in vitro growth of M. abscessus ; however, overexpression of the protein enhanced the uptake and survival of M. abscessus in THP-1 macrophages.

【 授权许可】

Unknown