Domain dissection and characterization of the aminoglycoside resistance enzyme ANT(3¡å)-Ii/AAC(6¡ä)-IId from Serratia marcescens

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• 作者：Keith D. Green^b ; Sylvie Garneau-Tsodikova^a ; ^b ; ^{sylviegt@umich.edu}
• 关键词：Acetyltransferase ; Aminoglycoside antibiotics ; Bacterial resistance ; Bifunctional enzyme ; Nucleotidyltransferase
• 刊名：Biochimie
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：95
• 期：6
• 页码：1319-1325
• 全文大小：551 K

文摘

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¡å)-Ii/AAC(6¡ä)-IId. To gain insight into the role, effect, and importance of the union of ANT(3¡å)-Ii and AAC(6¡ä)-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¡å)-Ii/AAC(6¡ä)-IId and its individually expressed components.