Gentamicin binds to the lectin site of calreticulin and inhibits its chaperone activity

Biochemical and Biophysical Research Communications
Tomohisa HoribeMasakazu Kikuchi

Abstract

Recently, it became clear that aminoglycoside antibiotics affect protein-protein interactions involving protein disulfide isomerase as well as protein synthesis in the endoplasmic reticulum. In this study, we used affinity column chromatography to screen gentamicin-binding proteins in microsomes derived from bovine kidney in order to learn about the possible mechanisms of gentamicin-associated nephrotoxicity. One of the gentamicin-binding proteins was identified as calreticulin (CRT) by N-terminal amino acid sequence analysis. Interestingly, gentamicin inhibited the chaperone and oxidative refolding activities of CRT when N-glycosylated substrates such as alpha1-antitrypsin and alpha-mannosidase were used as substrates, but it did not inhibit the chaperone activity of CRT when unglycosylated citrate synthase was used. Moreover, CRT suppressed the aggregation of deglycosylated and denatured alpha-mannosidase, but gentamicin did not inhibit its chaperone activity. Experiments with domain mutants suggest that the lectin site of CRT is the main target for gentamicin binding and that binding of gentamicin to this site inhibits the chaperone activity of CRT.

References

May 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·M LaMantiaT Mizunaga
Aug 1, 1973·Analytical Biochemistry·O TangenS Orrenius
Jan 27, 1995·The Journal of Biological Chemistry·D P SingalS A Quadri
Feb 21, 1997·Cell·K H Krause, M Michalak
May 2, 2000·The Journal of Biological Chemistry·F ShaoJ C Bardwell
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·L EllgaardK Wüthrich
Aug 29, 2001·The Journal of Cell Biology·K NakamuraM Michalak
Dec 14, 2001·Biochemical and Biophysical Research Communications·T HoribeM Kikuchi
Jun 8, 2002·The Journal of Biological Chemistry·Michael R LeachDavid B Williams
Jul 26, 2002·The Journal of Antibiotics·Tomohisa HoribeMasakazu Kikuchi
Sep 3, 2002·Journal of Biochemistry·Masakazu KikuchiYoshiyuki Tsujimoto
Nov 20, 2003·American Journal of Physiology. Renal Physiology·Ruben M Sandoval, Bruce A Molitoris
Feb 18, 2004·The Journal of Biological Chemistry·Toshio MiyazakiHideaki Itoh

❮ Previous
Next ❯

Citations

Nov 17, 2011·Journal of Molecular Modeling·Gururao HariprasadAlagiri Srinivasan
Mar 4, 2009·Journal of the Association for Research in Otolaryngology : JARO·Qi Wang, Peter S Steyger
Oct 31, 2007·Apoptosis : an International Journal on Programmed Cell Death·H ServaisM-P Mingeot-Leclercq
Oct 17, 2013·Chemical Research in Toxicology·Maralise Perigolo de OliveiraJean-Luc Décout
Jul 30, 2011·Integrative Biology : Quantitative Biosciences From Nano to Macro·Takatoshi Karasawa, Peter S Steyger
Sep 11, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yaremi QuirosFrancisco J López-Hernández
Mar 30, 2006·Antimicrobial Agents and Chemotherapy·Hélène ServaisMarie-Paule Mingeot-Leclercq
Jul 26, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Takatoshi KarasawaPeter S Steyger
Nov 1, 2005·Drug Metabolism Reviews·Alastair E CribbLaetitia Schneider
Mar 1, 2012·Kidney International Supplements
Sep 24, 2010·Kidney International·Jose M Lopez-NovoaFrancisco J Lopez-Hernandez
Apr 10, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Mathieu Peyrou, Alastair E Cribb
Apr 23, 2005·Biochemical and Biophysical Research Communications·Taiji KimuraMasakazu Kikuchi
May 15, 2015·Cell Death & Disease·P Garcia-HuertaC Hetz
Aug 13, 2011·Free Radical Biology & Medicine·Sophie DenamurMarie-Paule Mingeot-Leclercq
Mar 6, 2015·Frontiers in Cellular Neuroscience·Tamara M StawickiEdwin W Rubel
Oct 25, 2017·Frontiers in Cellular Neuroscience·Meiyan JiangPeter S Steyger

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.