Analysis of the human kinome using methods including fold recognition reveals two novel kinases.

TitleAnalysis of the human kinome using methods including fold recognition reveals two novel kinases.
Publication TypeJournal Article
Year of Publication2008
AuthorsBriedis KM, Starr A, Bourne PE
JournalPLoS One
Volume3
Issue2
Paginatione1597
Date Published2008
ISSN1932-6203
KeywordsAmino Acid Sequence, Computational Biology, Humans, Protein Conformation, Protein Kinases, Proteins, Proteome, Software
Abstract

BACKGROUND: Protein sequence similarity is a commonly used criterion for inferring the unknown function of a protein from a protein of known function. However, proteins can diverge significantly over time such that sequence similarity is difficult, if not impossible, to find. In some cases, a structural similarity remains over long evolutionary time scales and once detected can be used to predict function.

METHODOLOGY/PRINCIPAL FINDINGS: Here we employed a high-throughput approach to assign structural and functional annotation to the human proteome, focusing on the collection of human protein kinases, the human kinome. We compared human protein sequences to a library of domains from known structures using WU-BLAST, PSI-BLAST, and 123D. This approach utilized both sequence comparison and fold recognition methods. The resulting set of potential protein kinases was cross-checked against previously identified human protein kinases, and analyzed for conserved kinase motifs.

CONCLUSIONS/SIGNIFICANCE: We demonstrate that our structure-based method can be used to identify both typical and atypical human protein kinases. We also identify two potentially novel kinases that contain an interesting combination of kinase and acyl-CoA dehydrogenase domains.

DOI10.1371/journal.pone.0001597
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/18270584?dopt=Abstract
PMCPMC2223070
Alternate JournalPLoS ONE
PubMed ID18270584