L Rychlewski1, B Zhang, A Godzik. 1. Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Abstract
BACKGROUND: Uncharacterized proteins from newly sequenced genomes provide perfect targets for fold and function prediction. RESULTS: For 38% of the entire genome of Mycoplasma genitalium, sequence similarity to a protein with a known structure can be recognized using a new sequence alignment algorithm. When comparing genomes of M. genitalium and Escherichia coli, > 80% of M. genitalium proteins have a significant sequence similarity to a protein in E. coli and there are > 40 examples that have not been recognized before. For all cases of proteins with significant profile similarities, there are strong analogies in their functions, if the functions of both proteins are known. The results presented here and other recent results strongly support the argument that such proteins are actually homologous. Assuming this homology allows one to make tentative functional assignments for > 50 previously uncharacterized proteins, including such intriguing cases as the putative beta-lactam antibiotic resistance protein in M. gentalium. CONCLUSIONS: Using a new profile-to-profile alignment algorithm, the three-dimensional fold can be predicted for almost 40% of proteins from a genome of the small bacterium M. genitalium, and tentative function can be assigned to almost 80% of the entire genome. Some predictions lead to new insights about known functions or point to hitherto unexpected features of M. genitalium.
BACKGROUND: Uncharacterized proteins from newly sequenced genomes provide perfect targets for fold and function prediction. RESULTS: For 38% of the entire genome of Mycoplasma genitalium, sequence similarity to a protein with a known structure can be recognized using a new sequence alignment algorithm. When comparing genomes of M. genitalium and Escherichia coli, > 80% of M. genitalium proteins have a significant sequence similarity to a protein in E. coli and there are > 40 examples that have not been recognized before. For all cases of proteins with significant profile similarities, there are strong analogies in their functions, if the functions of both proteins are known. The results presented here and other recent results strongly support the argument that such proteins are actually homologous. Assuming this homology allows one to make tentative functional assignments for > 50 previously uncharacterized proteins, including such intriguing cases as the putative beta-lactam antibiotic resistance protein in M. gentalium. CONCLUSIONS: Using a new profile-to-profile alignment algorithm, the three-dimensional fold can be predicted for almost 40% of proteins from a genome of the small bacterium M. genitalium, and tentative function can be assigned to almost 80% of the entire genome. Some predictions lead to new insights about known functions or point to hitherto unexpected features of M. genitalium.