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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances of Heterocyclic Chemistry with Pesticide Activity
Global food safety and security will continue to be a global concern for the next 50 years and beyond. Plant diseases have had a significant impact on food safety and security throughout the entire food chain, from primary production to consumption. While conventional chemical pesticides have been traditionally used for ...read more
Calculation design of covalent/metal organic framework based catalysts
This research area combines theoretical computation and screening with machine learning for the design of covalent/metal organic framework-based catalysts, bridging the disciplines of organic chemistry, physical chemistry, computational chemistry, materials science, and machine learning. It covers several critical aspects: designing and synthesizing organic catalysts for improved performance, applying computational methods ...read more
Carbohydrates conversion in biofuels and bioproducts
Biomass pretreatment, hydrolysis, and saccharification of carbohydrates, and sugars bioconversion in biofuels and bioproducts within a biorefinery framework. Carbohydrates derived from woody biomass, agricultural wastes, algae, sewage sludge, or any other lignocellulosic feedstock are included in this issue. Simulation, techno-economic analysis, and life cycle analysis of a biorefinery process are ...read more
Catalytic C-H bond activation as a tool for functionalization of heterocycles
The major topic is the functionalization of heterocycles through catalyzed C-H bond activation. The strategies based on C-H activation not only provide straightforward formation of C-C or C-X bonds but, more importantly, allow for the avoidance of pre-functionalization of one or two of the cross-coupling partners. The beneficial impact of ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Cellular Membranes and Lipid-Binding Domains as Attractive Targets for Drug Development
Current Drug Targets Recent Patents on Biomedical Devices and Nanomaterials for Hyperthermal Therapy of Cancer
Recent Patents on Nanomedicine Increased Risk of Falls, Fall-related Injuries and Fractures in People with Type 1 and Type 2 Diabetes - A Nationwide Cohort Study
Current Drug Safety Interleukin-4-Induced Oxidative Stress Via Microglial NADPH Oxidase Contributes to the Death of Hippocampal Neurons In Vivo
Current Aging Science The Potential of Trace Amines and Their Receptors for Treating Neurological and Psychiatric Diseases
Reviews on Recent Clinical Trials Patent Selections
Recent Patents on Computer Science Madecassic Acid Reduces Fast Transient Potassium Channels and Promotes Neurite Elongation in Hippocampal CA1 Neurons
CNS & Neurological Disorders - Drug Targets Meningitis Due to Cryptococcus neoformans: Treatment with Posaconazole
Current HIV Research Regulators of Platelet cAMP Levels: Clinical and Therapeutic Implications
Current Medicinal Chemistry Potentials of ES Cell Therapy in Neurodegenerative Diseases
Current Pharmaceutical Design Safety and Efficacy of Levetiracetam for the Management of Levodopa- Induced Dyskinesia in Patients with Parkinson’s Disease: A Systematic Review
CNS & Neurological Disorders - Drug Targets Patent Selections:
Recent Patents on Inflammation & Allergy Drug Discovery Role of Monocarboxylate Transporters in Drug Delivery to the Brain
Current Pharmaceutical Design Melatonin in Autism Spectrum Disorders
Current Clinical Pharmacology mTOR Inhibitors in Tuberous Sclerosis Complex
Current Neuropharmacology From Genomic Imprinting to Developmental Physiology: Identifying Stepping Stones
Current Pharmacogenomics Clinical Observation of Electroencephalographic Changes and Risk of Convulsion Occurrence in Children Receiving Neural Precursor Cell Transplantation
CNS & Neurological Disorders - Drug Targets Towards the Molecular Foundations of Glutamatergic-targeted Antidepressants
Current Neuropharmacology Prader-Willi Syndrome: Genetics, Phenotype, and Management
Current Psychiatry Reviews Molecule of the Month
Current Topics in Medicinal Chemistry