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

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 mycoba...

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Autores principales:	Bálint Mészáros, Judit Tóth, Beáta G Vértessy, Zsuzsanna Dosztányi, István Simon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1fa61ac5b19c4e768dd54fc9b04c8cef
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spelling	oai:doaj.org-article:1fa61ac5b19c4e768dd54fc9b04c8cef2021-11-18T05:50:24ZProteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.1553-734X1553-735810.1371/journal.pcbi.1002118https://doaj.org/article/1fa61ac5b19c4e768dd54fc9b04c8cef2011-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21814507/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Lengthy 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.Bálint MészárosJudit TóthBeáta G VértessyZsuzsanna DosztányiIstván SimonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 7, p e1002118 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Bálint Mészáros Judit Tóth Beáta G Vértessy Zsuzsanna Dosztányi István Simon Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.
description	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.
format	article
author	Bálint Mészáros Judit Tóth Beáta G Vértessy Zsuzsanna Dosztányi István Simon
author_facet	Bálint Mészáros Judit Tóth Beáta G Vértessy Zsuzsanna Dosztányi István Simon
author_sort	Bálint Mészáros
title	Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.
title_short	Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.
title_full	Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.
title_fullStr	Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.
title_full_unstemmed	Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.
title_sort	proteins with complex architecture as potential targets for drug design: a case study of mycobacterium tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/1fa61ac5b19c4e768dd54fc9b04c8cef
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Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.

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