Abstract
Tuberculosis has become one of the deadliest global emergencies due to the widespread existence of multiple drug resistance strains of Mycobacterium tuberculosis and the increase of immuno-compromised populations in large parts of the world. Although the complete genome of M. tuberculosis became available in 1998, opening unprecedented opportunities for target-specific drug development, the progress since then has been slow, mainly due to a lack of a sufficiently strong interest by pharmaceutical and biotechnology industries. One of the most promising tools for future drug discovery lies in the elucidation of the molecular structures of potential drug targets from the M. tuberculosis proteome. During the last five years, the structures of about 200 unique targets have already been determined, which comprise about 5% of the entire M. tuberculosis proteome. As an example, we present the approach and some of the key achievements of the X-MTB consortium based in Germany. We summarize and discuss some recent highlights of potential drug targets of M. tuberculosis involved in lipid metabolism, protein phosphorylation/dephosphorylation and amino acid biosynthesis. The achievements of several structural genomics consortia that focus on targets from the M. tuberculosis proteome are now providing a solid framework to support coordinated international approaches for future structure-based drug discovery programs at the interface between industrial enterprises and academic research. One of the objectives will be to focus on target complexes, in addition to single targets that dominate the present repository of structures from the M. tuberculosis proteome.
Keywords: Bacillus Calmette-Guerin, Mtb genome sequences, Acyl-coA carboxylase, Open-reading frame, amino acid biosynthesis
Current Protein & Peptide Science
Title: Structure-Based Approaches to Drug Discovery Against Tuberculosis
Volume: 8 Issue: 4
Author(s): Simon J. Holton, Manfred S. Weiss, Paul A. Tucker and Matthias Wilmanns
Affiliation:
Keywords: Bacillus Calmette-Guerin, Mtb genome sequences, Acyl-coA carboxylase, Open-reading frame, amino acid biosynthesis
Abstract: Tuberculosis has become one of the deadliest global emergencies due to the widespread existence of multiple drug resistance strains of Mycobacterium tuberculosis and the increase of immuno-compromised populations in large parts of the world. Although the complete genome of M. tuberculosis became available in 1998, opening unprecedented opportunities for target-specific drug development, the progress since then has been slow, mainly due to a lack of a sufficiently strong interest by pharmaceutical and biotechnology industries. One of the most promising tools for future drug discovery lies in the elucidation of the molecular structures of potential drug targets from the M. tuberculosis proteome. During the last five years, the structures of about 200 unique targets have already been determined, which comprise about 5% of the entire M. tuberculosis proteome. As an example, we present the approach and some of the key achievements of the X-MTB consortium based in Germany. We summarize and discuss some recent highlights of potential drug targets of M. tuberculosis involved in lipid metabolism, protein phosphorylation/dephosphorylation and amino acid biosynthesis. The achievements of several structural genomics consortia that focus on targets from the M. tuberculosis proteome are now providing a solid framework to support coordinated international approaches for future structure-based drug discovery programs at the interface between industrial enterprises and academic research. One of the objectives will be to focus on target complexes, in addition to single targets that dominate the present repository of structures from the M. tuberculosis proteome.
Export Options
About this article
Cite this article as:
Simon J. Holton , Manfred S. Weiss , Paul A. Tucker and Matthias Wilmanns , Structure-Based Approaches to Drug Discovery Against Tuberculosis, Current Protein & Peptide Science 2007; 8 (4) . https://dx.doi.org/10.2174/138920307781369445
DOI https://dx.doi.org/10.2174/138920307781369445 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...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
Related Articles
-
Cytokines as a Therapeutic Target for Allergic Diseases: A Complex Picture
Current Pharmaceutical Design Identification of Drug Targets in Helicobacter pylori by in silico Analysis : Possible Therapeutic Implications for Gastric cancer
Current Cancer Drug Targets Atherosclerosis as an Inflammatory Disease
Current Pharmaceutical Design Preclinical Study of New TB Drugs and Drug Combinations in Mouse Models
Recent Patents on Anti-Infective Drug Discovery Identification of Anti-cancer Peptides Based on Multi-classifier System
Combinatorial Chemistry & High Throughput Screening Anti-Inflammatory Drugs in Psychiatry
Inflammation & Allergy - Drug Targets (Discontinued) A QSAR Study of Biphenyl Analogues of 2-Nitroimidazo-[2, 1-b] [1, 3] - oxazines as Antitubercular Agents Using Genetic Function Approximation
Medicinal Chemistry Current Understanding on Biosynthesis of Microbial Polysaccharides
Current Topics in Medicinal Chemistry Structure-Activity Design, Synthesis and Biological Activity of Newer Imidazole- Triazine Clubbed Derivatives as Antimicrobial and Antitubercular Agents
Letters in Organic Chemistry Recent Advances in Thymidine Kinase 2 (TK2) Inhibitors and New Perspectives for Potential Applications
Current Pharmaceutical Design Design, Synthesis and Biological Evaluation of Novel Tetrahydroquinoline Based Propanehydrazides as Antitubercular Agents
Letters in Drug Design & Discovery Design and In Vitro Evaluation of Five Inhibitors of Mycobacterium Tuberculosis
Letters in Drug Design & Discovery Review of Structures Containing Fullerene-C60 for Delivery of Antibacterial Agents. Multitasking model for Computational Assessment of Safety Profiles
Current Bioinformatics Review of Current Chemoinformatic Tools for Modeling Important Aspects of CYPsmediated Drug Metabolism. Integrating Metabolism Data with Other Biological Profiles to Enhance Drug Discovery
Current Drug Metabolism Synthesis, Anticonvulsant and Antimicrobial Activities of Some New [1-(2-Naphthyl)-2-(pyrazol-1-yl)ethanone]oxime Ethers
Medicinal Chemistry Electroporation Gene Therapy: New Developments In Vivo and In Vitro
Current Gene Therapy Bioactivity of Chitosan and Its Derivatives
Current Organic Chemistry Tuberculosis and its Treatment: An Overview
Mini-Reviews in Medicinal Chemistry Multi-Target-Directed Ligands as Innovative Tools to Combat Trypanosomatid Diseases
Current Topics in Medicinal Chemistry Development of a Multi-Compartmental Oral Vaccine Delivery System
Drug Delivery Letters