Backbone resonance assignments of a promiscuous aminoglycoside antibiotic resistance enzyme; the aminoglycoside phosphotransferase(3')-IIIa

Date

2010-04-01

Author

Serpersu, Engin H.
Özen, Can
Norris, Adrianne L.
Steren, Carlos
Whittemore, Neil

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

157
views

0
downloads

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. Moreover, the number of observable peaks and their dispersion in HSQC spectra varies with each aminoglycoside, rendering the resonance assignments very challenging. Therefore, the binary APH-tobramycin complex, which shows the largest number of well-resolved peaks, was used for the backbone resonance assignments (C alpha, C, N, H, and some C beta) of this protein (BMRB-16337).

Subject Keywords

Antibiotic Resistance, Aminoglycoside, Phosphotransferase, Backbone Resonance, Assignments, Promiscuous Enzyme

URI

https://hdl.handle.net/11511/31324

Journal

BIOMOLECULAR NMR ASSIGNMENTS

DOI

https://doi.org/10.1007/s12104-009-9195-z

Collections

Graduate School of Natural and Applied Sciences, Article

Suggestions

OpenMETU
Core

Studies of enzymes that cause resistance to aminoglycosides antibiotics. Serpersu, Engin H; Özen, Can; Wright, Edward (2008-01-01) 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 ...
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...
SYNTHESIS OF NOVEL MATERIALS FOR HIGH PERFORMANCE POLYMERIC MEMBRANE APPLICATIONS TUL MUNNA, SADIA; Akdağ, Akın; Çulfaz Emecen, Pınar Zeynep; Department of Polymer Science and Technology (2021-9-10) The polymeric membranes for antimicrobial applications are in high demand nowadays, since the bacteria had developed the resistance against the antibiotics. The membrane technology could become an efficient tool to cope with the antibiotic resistant bacteria which are becoming an unevitable problem on the health and pocket of a common man. To address this issue, the current research is carried out to synthesize polymer with antibacterial properties. Norbornene and oxonorborne monomers with special modificat...
Determination of colistin resistance in Escherichia coli isolates from foods in Turkey, 2011-2015 Güzel, Mustafa; Avşaroğlu, M Dilek; Soyer, Yeşim (2020-05-01) Antimicrobial resistance of pathogenic microorganisms is an emerging public health concern. Intensive use of antibiotics in food animals might increase antimicrobial resistance in foodborne pathogens. Colistin is a last resort antibiotic for treatment of multidrug resistant (MDR) Gram negative pathogens. The recent antimicrobial resistance studies revealed a mobile antimicrobial resistance gene (mcr) that provides resistance to colistin. Furthermore, the gene has been found in different genera. Therefore, t...
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, A. L. Norris, C. Steren, and N. Whittemore, “Backbone resonance assignments of a promiscuous aminoglycoside antibiotic resistance enzyme; the aminoglycoside phosphotransferase(3′)-IIIa,” BIOMOLECULAR NMR ASSIGNMENTS, pp. 9–12, 2010, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/31324.