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

Alsarraf, HMAB; Ung, KL; Johansen, MD; Dimon, J; Olieric, V; Kremer, L; Blaise, M

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

Alsarraf, HMAB Ung, KL Johansen, MD Dimon, J Olieric, V Kremer, L Blaise, M

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Publisher:: Federation of European Biochemical Societies
Publication Type:: Journal Article
Citation:: FEBS Letters, 2022, 596, (12), pp. 1516-1532
Issue Date:: 2022-06

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Field	Value	Language
dc.contributor.author	Alsarraf, HMAB
dc.contributor.author	Ung, KL
dc.contributor.author	Johansen, MD
dc.contributor.author	Dimon, J
dc.contributor.author	Olieric, V
dc.contributor.author	Kremer, L
dc.contributor.author	Blaise, M
dc.date.accessioned	2022-12-14T01:54:22Z
dc.date.available	2022-04-07
dc.date.available	2022-12-14T01:54:22Z
dc.date.issued	2022-06
dc.identifier.citation	FEBS Letters, 2022, 596, (12), pp. 1516-1532
dc.identifier.issn	0014-5793
dc.identifier.issn	1873-3468
dc.identifier.uri	http://hdl.handle.net/10453/164389
dc.description.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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Federation of European Biochemical Societies
dc.relation.ispartof	FEBS Letters
dc.relation.isbasedon	10.1002/1873-3468.14360
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 0603 Evolutionary Biology
dc.subject.classification	Biochemistry & Molecular Biology
dc.subject.mesh	Acetyltransferases
dc.subject.mesh	Mycobacterium
dc.subject.mesh	Mycobacterium abscessus
dc.subject.mesh	Tandem Repeat Sequences
dc.subject.mesh	Virulence
dc.subject.mesh	Acetyltransferases
dc.subject.mesh	Mycobacterium
dc.subject.mesh	Mycobacterium abscessus
dc.subject.mesh	Tandem Repeat Sequences
dc.subject.mesh	Virulence
dc.subject.mesh	Mycobacterium
dc.subject.mesh	Acetyltransferases
dc.subject.mesh	Virulence
dc.subject.mesh	Tandem Repeat Sequences
dc.subject.mesh	Mycobacterium abscessus
dc.title	Biochemical, structural, and functional studies reveal that MAB_4324c from Mycobacterium abscessus is an active tandem repeat N-acetyltransferase.
dc.type	Journal Article
utslib.citation.volume	596
utslib.location.activity	England
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	0603 Evolutionary Biology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	in_progress	*
pubs.consider-herdc	false
dc.date.updated	2022-12-14T01:54:21Z
pubs.issue	12
pubs.publication-status	Published
pubs.volume	596
utslib.citation.issue	12

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/164389