Nucleoside triphosphate cosubstrates control the substrate profile and efficiency of aminoglycoside 3'-O -phosphotransferase type IIa

MedChemComm
Selina Y L HolbrookSylvie Garneau-Tsodikova

Abstract

Aminoglycosides (AGs) are broad-spectrum antibiotics that play an important role in the control and treatment of bacterial infections. Despite the great antibacterial potency of AGs, resistance to these antibiotics has limited their clinical applications. The AG 3'-O-phosphotransferase of type IIa (APH(3')-IIa) encoded by the neoR gene is a common bacterial AG resistance enzyme that inactivates AG antibiotics. This enzyme is used as a selection marker in molecular biology research. APH(3')-IIa catalyzes the transfer of the γ-phosphoryl group of ATP to an AG at its 3'-OH group. Although APH(3')-IIa has been reported to utilize exclusively ATP as a cosubstrate, we demonstrate that this enzyme can utilize a broad array of NTPs. By substrate profiling, TLC, and enzyme kinetics experiments, we probe AG phosphorylation by APH(3')-IIa with an extensive panel of substrates and cosubstrates (13 AGs and 10 NTPs) for the purpose of gaining a thorough understanding of this resistance enzyme. We find, for the first time, that the identity of the NTP cosubstrate dictates the set of AGs modified by APH(3')-IIa and the phosphorylation efficiency for different AGs.

References

May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R L YenofskyJ W Pellow
Oct 20, 1995·The Journal of Biological Chemistry·G A McKay, G D Wright
May 15, 2002·The EMBO Journal·Desiree H Fong, Albert M Berghuis
Mar 17, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ming DuDavid M Bedwell
Oct 22, 2008·Trends in Genetics : TIG·Liat Linde, Batsheva Kerem
Nov 10, 2009·Chembiochem : a European Journal of Chemical Biology·Keith D GreenSylvie Garneau-Tsodikova
Mar 17, 2010·Antimicrobial Agents and Chemotherapy·Tushar Shakya, Gerard D Wright
Apr 17, 2010·Chembiochem : a European Journal of Chemical Biology·Jacob L HoughtonSylvie Garneau-Tsodikova
Sep 14, 2010·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Maria S Ramirez, Marcelo E Tolmasky
Apr 7, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christophe PichavantJacques P Tremblay
Nov 7, 2012·Antimicrobial Agents and Chemotherapy·Marta TothSergei B Vakulenko
Jul 19, 2013·Future Medicinal Chemistry·Kristin J Labby, Sylvie Garneau-Tsodikova
Nov 21, 2013·American Journal of Respiratory Cell and Molecular Biology·Xiaojiao XueSteven M Rowe
Jul 30, 2014·MedChemComm·Marina Y FossoSylvie Garneau-Tsodikova
May 6, 2015·Antimicrobial Agents and Chemotherapy·Yijia LiSylvie Garneau-Tsodikova
Dec 1, 2015·ACS Medicinal Chemistry Letters·Nishad Thamban ChandrikaSylvie Garneau-Tsodikova
Feb 16, 2016·MedChemComm·Sylvie Garneau-Tsodikova, Kristin J Labby
Sep 13, 2016·Biochemistry·Selina Y L Holbrook, Sylvie Garneau-Tsodikova
Apr 5, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dámaso Sánchez-CarreraCarlos Pipaón
Dec 21, 2017·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Selina Y L Holbrook, Sylvie Garneau-Tsodikova

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Methods Mentioned

BETA
PCR
column chromatography

Software Mentioned

SigmaPlot
SysStat

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