Biochemical, structural, and functional studies reveal that MAB_4324c from Mycobacterium abscessus is an active tandem repeat N‐acetyltransferase. Issue 12 (3rd June 2022)

• Record Type: Journal Article
• Authors: Alsarraf, Husam M. A. B.; Ung, Kien Lam; Johansen, Matt D.; Dimon, Juliette; Olieric, Vincent; Kremer, Laurent; Blaise, Mickaël
• Is Part Of: FEBS letters. Volume 596:Issue 12(2022)
• Page Start: 1516
• Page End: 1532
• Publication Date: 2022-06-03
• Subjects: GCN5 -- infection -- intracellular survival -- macrophage -- Mycobacterium abscessus -- N‐acetyltransferase -- X‐ray structure; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14360
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract : We report the characterization of the atypical tandem repeat N ‐acetyltransferase MAB_4324c from Mycobacterium abscessus . The protein can acetylate small polyamine substrates such as spermidine. The X‐ray structure of MAB_4324c revealed an unexpected NADH/NADPH molecule bound to the N‐terminal GCN5‐related N ‐acetyltransferase domain. Furthermore, M. abscessus strains overexpressing MAB_4324c displayed enhanced intracellular survival in human macrophages as compared to the wild‐type strain.