PMID: 9545431May 23, 1998Paper

Active-site mutants of the VanC2 D-alanyl-D-serine ligase, characteristic of one vancomycin-resistant bacterial phenotype, revert towards wild-type D-alanyl-D-alanine ligases

Chemistry & Biology
V L HealyC T Walsh

Abstract

The rising number of vancomycin-resistant enterococci (VREs) is a major concern to modern medicine because vancomycin is currently the 'last resort' drug for life-threatening infections. The D-alanyl-D-X ligases (where X is an hydroxy or amino acid) of bacteria catalyze a critical step in bacterial cell-wall peptidoglycan assembly. In bacteria that produce glycopeptide antibiotics and in opportunistic pathogens, including VREs, D-, D-ligases serve as switches that confer antibiotic resistance on the bacteria themselves. Peptidoglycans in vancomycin-sensitive bacteria end in D-alanyl-D-alanine, whereas in vancomycin-resistant bacteria they end in D-alanyl-D-lactate or D-alanyl-D-serine. We demonstrate that the selective utilization of D-serine by the Enterococcus casseliflavus VanC2 ligase can be altered by mutagenesis of one of two residues identified by homology to the X-ray structure of the Escherichia coli D-alanyl-Dalanine ligase (DdlB). The Arg322-->Met (R322M) and Phe250-->Tyr (F250Y) ligase mutants show a 36-44-fold decrease in the use of D-serine, as well as broadened specificity for utilization of other D-amino acids in place of D-serine. The F250Y R322M double mutant is effectively disabled as a D-alanyl-D-serine liga...Continue Reading

References

Sep 1, 1992·Antimicrobial Agents and Chemotherapy·R LeclercqP Courvalin
Jul 1, 1995·Antimicrobial Agents and Chemotherapy·D F SahmS Handwerger
Jul 1, 1994·The Biochemical Journal·P E ReynoldsP Courvalin
Aug 1, 1993·Antimicrobial Agents and Chemotherapy·M Arthur, P Courvalin
Nov 7, 1996·The New England Journal of Medicine·H S Gold, R C Moellering
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·C G MarshallG D Wright
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·I S ParkC T Walsh

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Citations

Feb 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Phillip H A LeeRichard L Gallo
Apr 23, 2011·Bioscience, Biotechnology, and Biochemistry·Tomoki NakagawaKuniki Kino
Dec 24, 2004·Antimicrobial Agents and Chemotherapy·Peter E Reynolds, Patrice Courvalin
Oct 24, 2009·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Patrick WeberPatrice Courvalin
Feb 17, 2009·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Shojiro WatanabeNaoki Watanabe
Nov 9, 2006·Bioscience, Biotechnology, and Biochemistry·Masaru SatoKuniki Kino
Oct 20, 2005·Journal of Bioscience and Bioengineering·Masaru SatoKuniki Kino
Sep 13, 2012·The Journal of Biological Chemistry·Djalal Meziane-CherifPatrice Courvalin
Aug 14, 2020·Canadian Journal of Microbiology·Shikha Kapil, Vipasha Sharma

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