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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Acetyltransferases / antagonists & inhibitors
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Acetyltransferases / chemistry*
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Acetyltransferases / metabolism*
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Amino Acid Sequence
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Anabaena variabilis / enzymology*
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Anabaena variabilis / metabolism*
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Angiotensin-Converting Enzyme Inhibitors / chemistry
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Angiotensin-Converting Enzyme Inhibitors / pharmacology
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Antigens, Bacterial / chemistry*
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Antigens, Bacterial / metabolism
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Bacterial Proteins / antagonists & inhibitors
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Bacterial Proteins / chemistry*
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Bacterial Proteins / metabolism
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Binding Sites
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Computer Simulation
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Drug Resistance, Bacterial
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Kanamycin / analogs & derivatives
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Kanamycin / metabolism
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Kanamycin / pharmacology
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Kinetics
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Models, Molecular
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Molecular Sequence Data
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Mycobacterium smegmatis / enzymology
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Mycobacterium smegmatis / metabolism
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Mycobacterium tuberculosis / enzymology
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Mycobacterium tuberculosis / metabolism
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Phylogeny
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Sequence Alignment
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Substrate Specificity
Substances
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Angiotensin-Converting Enzyme Inhibitors
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Antigens, Bacterial
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Bacterial Proteins
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Kanamycin
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Acetyltransferases
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Eis protein, Mycobacterium tuberculosis
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aminoglycoside acetyltransferase