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Large‐scale survey for potentially targetable indels in bacterial and protozoan proteins
Author(s) -
Cherkasov Artem,
Lee ShangJung,
Nandan Devki,
Reiner Neil E.
Publication year - 2005
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20631
Subject(s) - indel , scale (ratio) , medicine , biology , genetics , geography , gene , genotype , single nucleotide polymorphism , cartography
Our previous results demonstrated that some essential, housekeeping proteins from pathogenic microorganisms may contain sizable insertions–deletions in their sequences (compared to close human homologs) that can be responsible for unexpected virulence properties. For example, we found that indel‐bearing elongation factor‐1α from several pathogenic protozoa can activate a human tyrosine phosphatase SHP‐1 leading to deactivation of macrophages. On the one hand, these findings allowed development of a strategy for targeting some indel‐containing pathogen proteins that have similar human counterparts. On the other hand, the results raised numerous questions regarding the nature and implications of sequence indels in pathogen proteins. In the present study, we conducted a large‐scale survey of indels in proteins from 136 bacterial and protozoan genomes. It has been established that sizable insertions and deletions occur in approximately 5–10% of bacterial proteins with close human homologs, while proteins from the protozoan pathogens such as Trypanosoma cruzi , Plasmodium falciparum , and Leishmania donovani exhibit elevated indel content that can reach up to 25%. The finding suggested that the occurrence of sequence indels may be involved in the evolution of pathogenic mechanisms in these protozoa. Proteins 2006. © 2005 Wiley‐Liss, Inc.