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

TY - JOUR

T1 - Biochemical, structural, and functional studies reveal that MAB_4324c from Mycobacterium abscessus is an active tandem repeat N-acetyltransferase

AU - Alsarraf, Husam M.A.B.

AU - Ung, Kien Lam

AU - Johansen, Matt D.

AU - Dimon, Juliette

AU - Olieric, Vincent

AU - Kremer, Laurent

AU - Blaise, Mickaël

N1 - Publisher Copyright: © 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

KW - GCN5

KW - infection

KW - intracellular survival

KW - macrophage

KW - Mycobacterium abscessus

KW - N-acetyltransferase

KW - X-ray structure

UR - http://www.scopus.com/inward/record.url?scp=85131157883&partnerID=8YFLogxK

U2 - 10.1002/1873-3468.14360

DO - 10.1002/1873-3468.14360

M3 - Journal article

C2 - 35470425

AN - SCOPUS:85131157883

SN - 0014-5793

VL - 596

SP - 1516

EP - 1532

JO - FEBS Letters

JF - FEBS Letters

IS - 12

ER -