title: Domain dissection and characterization of the aminoglycoside resistance enzyme ANT(3″)-Ii/AAC(6')-IId from Serratia marcescens.
abstract: Aminoglycosides (AGs) are broad-spectrum antibiotics whose constant use and presence in growth environments has led bacteria to develop resistance mechanisms to aid in their survival. A common mechanism of resistance to AGs is their chemical modification (nucleotidylation, phosphorylation, or acetylation) by AG-modifying enzymes (AMEs). Through evolution, fusion of two AME-encoding genes has resulted in bifunctional enzymes with broader spectrum of activity. Serratia marcescens, a human enteropathogen, contains such a bifunctional enzyme, ANT(3″)-Ii/AAC(6')-IId. To gain insight into the role, effect, and importance of the union of ANT(3″)-Ii and AAC(6')-IId in this bifunctional enzyme, we separated the two domains and compared their activity to that of the full-length enzyme. We performed a thorough comparison of the substrate and cosubstrate profiles as well as kinetic characterization of the bifunctional ANT(3″)-Ii/AAC(6')-IId and its individually expressed components.
authors.affiliation: Life Sciences Institute, 210 Washtenaw Ave, University of Michigan, Ann Arbor, MI 48109-2216, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Green
authors.forename: Sylvie
authors.initials: S
authors.lastname: Garneau-Tsodikova
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism*; D000617:Aminoglycosides; D001426:Bacterial Proteins; D004352:Drug Resistance, Microbial / Q000502:physiology*; D013058:Mass Spectrometry; D016133:Polymerase Chain Reaction; D012706:Serratia marcescens / Q000201:enzymology*
chemical_list: D000617:Aminoglycosides; D001426:Bacterial Proteins; D000123:Acetyltransferases