title: Biochemical and structural analysis of aminoglycoside acetyltransferase Eis from Anabaena variabilis.
abstract: The Mycobacterium tuberculosis enhanced intracellular survival (Eis_Mtb) protein is a clinically important aminoglycoside (AG) multi-acetylating enzyme. Eis homologues are found in a variety of mycobacterial and non-mycobacterial species. Variation of the residues lining the AG-binding pocket and positions of the loops bearing these residues in the Eis homologues dictates the substrate specificity and, thus, Eis homologues are Nature-made tools for elucidating principles of AG recognition by Eis. Here, we demonstrate that the Eis from Anabaena variabilis (Eis_Ava), the first non-mycobacterial Eis homologue reported, is a multi-acetylating AG-acetyltransferase. Eis_Ava, Eis from Mycobacterium tuberculosis (Eis_Mtb), and Eis from Mycobacterium smegmatis (Eis_Msm) have different structures of their AG-binding pockets. We perform comparative analysis of these differences and investigate how they dictate the substrate and cosubstrate recognition and acetylation of AGs by Eis.
authors.affiliation: University of Michigan, Life Sciences Institute, 210 Washtenaw Ave, Ann Arbor, MI 48109, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Pricer
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Houghton
authors.forename: Keith D
authors.initials: KD
authors.lastname: Green
authors.forename: Abdelrahman S
authors.initials: AS
authors.lastname: Mayhoub
authors.forename: Sylvie
authors.initials: S
authors.lastname: Garneau-Tsodikova
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D046870:Anabaena variabilis / Q000201:enzymology* / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003198:Computer Simulation; D024881:Drug Resistance, Bacterial; D007612:Kanamycin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020102:Mycobacterium smegmatis / Q000201:enzymology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000378:metabolism; D010802:Phylogeny; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007612:Kanamycin; D000123:Acetyltransferases; C430563:Eis protein, Mycobacterium tuberculosis; C019681:aminoglycoside acetyltransferase