Studies of enzymes that cause resistance to aminoglycosides antibiotics.

Serpersu, Engin H
Özen, Can
Wright, Edward
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.
Methods in molecular medicine


Backbone resonance assignments of a promiscuous aminoglycoside antibiotic resistance enzyme; the aminoglycoside phosphotransferase(3')-IIIa
Serpersu, Engin H.; Özen, Can; Norris, Adrianne L.; Steren, Carlos; Whittemore, Neil (2010-04-01)
The aminoglycoside phosphotransferase(3')-IIIa (APH) is a promiscuous enzyme and renders a large number of structurally diverse aminoglycoside antibiotics useless against infectious bacteria. A remarkable property of this similar to 31 kDa enzyme is in its unusual dynamic behavior in solution; the apo-form of the enzyme exchanges all of its backbone amide protons within 15 h of exposure to D (2) O while aminoglycoside-bound forms retain similar to 40% of the amide protons even after > 90 h of exposure. More...
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...
Determination of phenolic compound profiles and antioxidant effect of black elderberry, echinacea and iceland moss extracts on late-release soft lozenge
Yıldız, Özge; Bayındırlı, Alev; Çapanoğlu Güven, Esra; Department of Food Engineering (2021-6)
Medicinal plants contain different bioactive compounds that have immune system stimulant, anti-inflammatory, antibacterial, antiviral, antifungal, anticancer and wound healing effects. Echinacea purpurea L., Sambucus nigra L. and Cetraria islandica L. are known with their high antioxidant content and health promoting properties. The main objective of the study was to determine the total phenolic content, total flavonoid content and antioxidant capacity of each plant extract with water and 75 % ethanol as so...
Quantitative expression analysis of the genes potentially involved in clavulanic acid overproduction in streptomyces clavuligerus
Aktaş, Caner; Özcengiz, Gülay; Department of Molecular Biology and Genetics (2018)
Streptomyces clavuligerus is the producer of the medically important β-lactam antibiotics, including cephamycin C (CC) and the potent β-lactamase inhibitor clavulanic acid. (CA). We have already undertaken an extensive comparative proteomic analysis by using both 2-DE-MALDI-MS and GeLC-MS approaches between an industrial CA overproducer, namely DEPA and the reference strain NRRL3585. In this context, we documented several differentially expressed (over- and under-represented) proteins accounting for high CA...
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: