Domain dissection and characterization of the aminoglycoside resistance enzyme ANT(3″)-Ii/AAC(6′)-IId from Serratia marcescens |
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Authors: | Keith D Green Sylvie Garneau-Tsodikova |
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Institution: | 1. Department of Medicinal Chemistry, Life Sciences Institute, University of Michigan, 210 Washtenaw Ave, Room 4437, Ann Arbor, MI 48109-2216, USA;2. Life Sciences Institute, 210 Washtenaw Ave, University of Michigan, Ann Arbor, MI 48109-2216, USA |
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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. |
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Keywords: | Acetyltransferase Aminoglycoside antibiotics Bacterial resistance Bifunctional enzyme Nucleotidyltransferase |
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