Studies of enzymes that cause resistance to aminoglycosides antibiotics.

Date

2008-01-01

Author

Serpersu, Engin H
Özen, Can
Wright, Edward

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Aminoglycoside antibiotics are highly potent, wide-spectrum bactericidals (1, 2). Bacterial resistance to aminoglycosides, however, is a major problem in the clinical use of aminoglycosides. Enzymatic modification of aminoglycosides is the most frequent resistance mode among several resistance mechanisms employed by resistant pathogens (1,3). Three families of aminoglycoside modifying enzymes, O-phosphotransferases, N-acetyltransferases, and N-nucleotidyltransferases, are known to have more than 50 enzymes (1,3,4). In this chapter, determination of enzymatic activity of a single enzyme from each family in the presence and absence of an inhibitor is described.

Subject Keywords

Antibiotic resistance , Drug design, Enzyme inhibition, Aminoglycoside phosphotransferase, Aminoglycoside nucleotidyltransferase, Aminoglycoside acetyltransferase, Aminoglycosides

URI

https://hdl.handle.net/11511/57635

Journal

Methods in molecular medicine

DOI

https://doi.org/10.1007/978-1-59745-246-5_20

Collections

Graduate School of Natural and Applied Sciences, Article

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Discovery of non-carbohydrate inhibitors of aminoglycoside-modifying enzymes Welch, KT; Virga, KG; Whittemore, NA; Özen, Can; Wright, E; Brown, CL; Lee, RE; Serpersu, EH (2005-11-15) Chemical modification and inactivation of aminoglycosides by many different enzymes expressed in pathogenic bacteria are the main mechanisms of bacterial resistance to these antibiotics. In this work, we designed inhibitors that contain the 1,3-diamine pharmacophore shared by all aminoglycoside antibiotics that contain the 2-deoxystreptamine ring. A discovery library of molecules was prepared by attaching different side chains to both sides of the 1,3-diamine motif. Several of these diamines showed inhibito...
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Thermodynamics of aminoglycoside binding to aminoglycoside-3 '-phosphotransferase IIIa studied by isothermal titration calorimetry Özen, Can (2004-11-23) The aminoglycoside-3'-phosphotransferase IIIa [APH(3')-IIIIa] phosphorylates aminoglycoside antibiotics and renders them ineffective against bacteria. APH(3')-IIIa is the most promiscuous aminoglycoside phosphotransferase enzyme, and it modifies more than 10 different aminoglycoside antibiotics. A wealth of information exists about the enzyme; however, thermodynamic properties of enzyme-aminoglycoside complexes are still not known. This study describes the determination of the thermodynamic parameters of th...

Citation Formats

E. H. Serpersu, C. Özen, and E. Wright, “Studies of enzymes that cause resistance to aminoglycosides antibiotics.,” Methods in molecular medicine, pp. 261–271, 2008, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/57635.