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

Fetrow, JS Siew, N Di Gennaro, JA Martinez-Yamout, M Dyson, HJ Skolnick, J

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

40

INGLESE

Article

Biochemistry & Biophysics

PROTEIN SCIENCE

0961-8368 → ACNP

10

5

2001

1005 - 1014

ISI

0961-8368(200105)10:5<1005:GCOSAS>2.0.ZU;2-V

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.