Genomic-scale comparison of sequence- and structure-based methods of function prediction: Does structure provide additional insight?

Citation
Js. Fetrow et al., Genomic-scale comparison of sequence- and structure-based methods of function prediction: Does structure provide additional insight?, PROTEIN SCI, 10(5), 2001, pp. 1005-1014
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEIN SCIENCE
ISSN journal
0961-8368 → ACNP
Volume
10
Issue
5
Year of publication
2001
Pages
1005 - 1014
Database
ISI
SICI code
0961-8368(200105)10:5<1005:GCOSAS>2.0.ZU;2-V
Abstract
A function annotation method using the sequence-to-structure-to-function pa radigm is applied to the identification of all disulfide oxidoreductases in the Saccharomyces cerevisiae genome. The method identifies 27 sequences as potential disulfide oxidoreductases. All previously known thioredoxins, gl utaredoxins, and disulfide isomerases are correctly identified. Three of th e 27 predictions are probable false-positives. Three novel predictions, whi ch subsequently have been experimentally validated, are presented. Two addi tional novel predictions suggest a disulfide oxidoreductase regulatory mech anism for two subunits (OST3 and OST6) of the yeast oligosaccharyltransfera se complex. Based on homology, this prediction can be extended to a potenti al tumor suppressor gene, N33, in humans, whose biochemical function was no t previously known. Attempts to obtain a folded, active N33 construct to te st the prediction were unsuccessful. The results show that structure predic tion coupled with biochemically relevant structural motifs is a powerful me thod for the function annotation of genome sequences and can provide more d etailed, robust predictions than function prediction methods that rely on s equence comparison alone.