Abstract
D-amino acids are essential components of the bacterial cell wall and play notable roles in microbiology as regulators, for example in sporulation, biofilm formation or interspecies communication. Racemases are the specific enzymes catalyzing the interconversion of L-amino acids to D-amino acids. While most of racemases are mono-specific, a family of broad-spectrum racemases that can racemize ten of the 19 natural chiral amino acids has been recently reported. These enzymes can interconvert radically different residues such as aliphatic and positively charged residues producing non-canonical D-amino acids. Crystal structures together with bioinformatics allowed identification of the residues defining the molecular footprint in broad-spectrum racemases, the specific features of their active sites and the structural basis of their promiscuity. Here we review the recent knowledge on this family compared with the well established of alanine racemases. This structural information is a prerequisite for the development of novel drugs against the important human pathogens for which broadspectrum racemases play a key role.
Keywords: Non-canonical D-amino acids, racemases, bioinformatics; antibiotics resistance, X-ray crystallography.
Current Organic Chemistry
Title:Structural Bioinformatics in Broad-Spectrum Racemases: A New Path in Antimicrobial Research
Volume: 20 Issue: 11
Author(s): Noelia Bernardo-García, Pedro Sánchez-Murcia, Federico Gago, Felipe Cava and Juan A. Hermoso
Affiliation:
Keywords: Non-canonical D-amino acids, racemases, bioinformatics; antibiotics resistance, X-ray crystallography.
Abstract: D-amino acids are essential components of the bacterial cell wall and play notable roles in microbiology as regulators, for example in sporulation, biofilm formation or interspecies communication. Racemases are the specific enzymes catalyzing the interconversion of L-amino acids to D-amino acids. While most of racemases are mono-specific, a family of broad-spectrum racemases that can racemize ten of the 19 natural chiral amino acids has been recently reported. These enzymes can interconvert radically different residues such as aliphatic and positively charged residues producing non-canonical D-amino acids. Crystal structures together with bioinformatics allowed identification of the residues defining the molecular footprint in broad-spectrum racemases, the specific features of their active sites and the structural basis of their promiscuity. Here we review the recent knowledge on this family compared with the well established of alanine racemases. This structural information is a prerequisite for the development of novel drugs against the important human pathogens for which broadspectrum racemases play a key role.
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Cite this article as:
Bernardo-García Noelia, Sánchez-Murcia Pedro, Gago Federico, Cava Felipe and A. Hermoso Juan, Structural Bioinformatics in Broad-Spectrum Racemases: A New Path in Antimicrobial Research, Current Organic Chemistry 2016; 20 (11) . https://dx.doi.org/10.2174/1385272819666150810213115
DOI https://dx.doi.org/10.2174/1385272819666150810213115 |
Print ISSN 1385-2728 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5348 |
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