Abstract
Phospho-MurNAc-pentapeptide translocase (MraY, translocase I) catalyses the first step of the lipid-linked cycle of reactions of bacterial peptidoglycan biosynthesis. MraY is the target for five families of nucleoside antibacterial natural products: the tunicamycins, the mureidomycins (also pacidamycins, napsamycins), the liposidomycins, the muraymycins, and the capuramycins. Recent structure-activity studies on these families have led to the identification of active pharmacophores, and insight into their mechanisms of action. This step of peptidoglycan biosynthesis is also the target for the bacteriolytic E protein from bacteriophage φX174, and for cyclic peptides of the amphomycin family which complex the undecaprenyl phosphate co-substrate. The mechanisms of enzyme inhibition by these agents are discussed, and the state of knowledge regarding the transmembrane structure, active site, and catalytic mechanism of MraY. The availability of high throughput assays and prospects of MraY as an antibacterial target are also discussed.
Keywords: Peptidoglycan biosynthesis, antibacterial agents, MraY, high-throughput screening
Infectious Disorders - Drug Targets
Title: Phospho-MurNAc-Pentapeptide Translocase (MraY) as a Target for Antibacterial Agents and Antibacterial Proteins
Volume: 6 Issue: 2
Author(s): Timothy D.H. Bugg, Adrian J. Lloyd and David I. Roper
Affiliation:
Keywords: Peptidoglycan biosynthesis, antibacterial agents, MraY, high-throughput screening
Abstract: Phospho-MurNAc-pentapeptide translocase (MraY, translocase I) catalyses the first step of the lipid-linked cycle of reactions of bacterial peptidoglycan biosynthesis. MraY is the target for five families of nucleoside antibacterial natural products: the tunicamycins, the mureidomycins (also pacidamycins, napsamycins), the liposidomycins, the muraymycins, and the capuramycins. Recent structure-activity studies on these families have led to the identification of active pharmacophores, and insight into their mechanisms of action. This step of peptidoglycan biosynthesis is also the target for the bacteriolytic E protein from bacteriophage φX174, and for cyclic peptides of the amphomycin family which complex the undecaprenyl phosphate co-substrate. The mechanisms of enzyme inhibition by these agents are discussed, and the state of knowledge regarding the transmembrane structure, active site, and catalytic mechanism of MraY. The availability of high throughput assays and prospects of MraY as an antibacterial target are also discussed.
Export Options
About this article
Cite this article as:
Bugg D.H. Timothy, Lloyd J. Adrian and Roper I. David, Phospho-MurNAc-Pentapeptide Translocase (MraY) as a Target for Antibacterial Agents and Antibacterial Proteins, Infectious Disorders - Drug Targets 2006; 6 (2) . https://dx.doi.org/10.2174/187152606784112128
DOI https://dx.doi.org/10.2174/187152606784112128 |
Print ISSN 1871-5265 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3989 |
- 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
-
Monobactams: A Unique Natural Scaffold of Four-Membered Ring Skeleton, Recent Development to Clinically Overcome Infections by Multidrug- Resistant Microbes
Letters in Drug Design & Discovery Function Prediction of Hypothetical Proteins Without Sequence Similarity to Proteins of Known Function (SUPPLEMENTARY MATERIALS)
Protein & Peptide Letters Hybolites: Novel Therapeutic Tools for Targeting Hyperstructures in Bacteria
Recent Patents on Anti-Infective Drug Discovery Isoprenoid Biosynthesis of the Apicoplast as Drug Target
Current Drug Targets Antitubercular Drug Development: Current Status and Research Strategies
Mini-Reviews in Medicinal Chemistry Targeting Iron Acquisition by Mycobacterium tuberculosis
Infectious Disorders - Drug Targets Drug Delivery Systems with Modified Release for Systemic and Biophase Bioavailability
Current Clinical Pharmacology Subtracting Gene Function by Gene Silencing and Disruption in Bacteria
Current Biotechnology QSAR and Docking Studies of HCV NS3 Serine Protease Inhibitors
Medicinal Chemistry Signs and Related Mechanisms of Ethanol Hepatotoxicity
Current Drug Abuse Reviews Bioactive Metabolites from Pathogenic and Endophytic Fungi of Forest Trees
Current Medicinal Chemistry Synthesis, Characterization, Biological Activity and Voltammetric Behavior and Determination of Cefaclor Metal Complexes
Current Analytical Chemistry Novel Electrochemical Sensor for Rifampicin based on Ionic Liquid Functionalised TiO2 Nanoparticles
Current Analytical Chemistry Role of Old Antibiotics in Multidrug Resistant Bacterial Infections
Current Drug Targets Nanobiotechnological Approaches Against Multidrug Resistant Bacterial Pathogens: An Update
Current Drug Metabolism Dihydroartemisinin and its Analogs: A New Class of Antitubercular Agents
Current Topics in Medicinal Chemistry Non Nucleoside Reverse Transcriptase Inhibitors, Molecular Docking Studies and Antitubercular Activity of Thiazolidin-4-one Derivatives
Current Computer-Aided Drug Design Comparison of Protease Inhibitor (PI) Resistance-Associated Mutations Between PI-Naive and PI-Experienced HIV-1 Infected Patients in Thailand Where Subtype A/E is Predominant
Current HIV Research Relationship Between Carbapenems Structure and Minimal Inhibitory Concentration Selected Bacterial Strains
Letters in Drug Design & Discovery Antimicrobial Activity of 5-membered Nitroheteroaromatic Compounds beyond Nitrofurans and Nitroimidazoles: Recent Progress
Current Medicinal Chemistry