Structure-based assignment of the biochemical function of a hypothetical protein: A test case of structural genomics

Many small bacterial, archaebacterial, and eukaryotic genomes have been seq uenced, and the larger eukaryotic genomes are predicted to be completely se quenced within the next decade, In all genomes sequenced to date, a large p ortion of these organisms' predicted protein coding regions encode polypept ides of unknown biochemical, biophysical, and/or cellular functions, Three- dimensional structures of these proteins may suggest biochemical or biophys ical functions. Here we report the crystal structure of one such protein, M J0577 from a hyperthermophile, Methanococcus jannaschii, at 1.7-Angstrom re solution. The structure contains a hound ATP, suggesting MJ0577 is an ATPas e or an ATP-mediated molecular switch, which we confirm by biochemical expe riments, Furthermore, the structure reveals different ATP binding motifs th at are shared among many homologous hypothetical proteins in this family. T his result indicates that structure-based assignment of molecular function is a viable approach for the large-scale biochemical assignment of proteins and for discovering new motifs, a basic premise of structural genomics.