REAL

Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.

Mészáros, Bálint and Tóth, Judit and Vértessy G., Beáta and Dosztányi, Zsuzsanna and Simon, István (2011) Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis. PLOS COMPUTATIONAL BIOLOGY. ISSN 1553-734X

[img]
Preview
Text
7. journal.pcbi Proteins with complex.pdf

Download (510kB) | Preview

Abstract

Lengthy co-evolution of Homo sapiens and Mycobacterium tuberculosis, the main causative agent of tuberculosis, resulted in a dramatically successful pathogen species that presents considerable challenge for modern medicine. The continuous and ever increasing appearance of multi-drug resistant mycobacteria necessitates the identification of novel drug targets and drugs with new mechanisms of action. However, further insights are needed to establish automated protocols for target selection based on the available complete genome sequences. In the present study, we perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function specific to M. tuberculosis. We identified two families, termed pkn and PE/PPE that stand out in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteins involved in species-specific functions in a given organism. We conclude that target selection protocols should be extended to include proteins with complex domain architectures instead of focusing on sequentially unique and essential proteins only.

Item Type: Article
Subjects: Q Science / természettudomány > Q1 Science (General) / természettudomány általában
Depositing User: Dr Judit Tóth
Date Deposited: 23 Sep 2015 11:01
Last Modified: 23 Sep 2015 11:01
URI: http://real.mtak.hu/id/eprint/27433

Actions (login required)

Edit Item Edit Item