Crystal structure of YbaK protein from Haemophilus influenzae (HI1434) at 1.8 angstrom resolution: Functional implications

Structural genomics of proteins of unknown function most straightforwardly assists with assignment of biochemical activity when the new structure rese mbles that of proteins whose functions are known. When a new fold is reveal ed, the universe of known folds is enriched, and once the function is deter mined by other means, novel structure-function relationships are establishe d. The previously unannotated protein HI1434 from LT. influenzae provides a hybrid example of these two paradigms. It is a member of a microbial prote in family, labeled in SwissProt as YbaK and ebsC. The crystal structure at 1.8 Angstrom resolution reported here reveals a fold that is only remotely related to the C-lectin fold, in particular to endostatin, and thus is not sufficiently similar to imply that YbaK proteins are saccharide binding pro teins. However, a crevice that may accommodate a small ligand is evident, T he putative binding site contains only one invariant residue, Lys46, which carries a functional group that could play a role in catalysis, indicating that YbaK is probably not an enzyme. Detailed sequence analysis, including a number of newly sequenced microbial organisms, highlights sequence homolo gy to an insertion domain in prolyl-tRNA synthetases (proRS) from prokaryot e, a domain whose function is unknown. A HI1434-based model of the insertio n domain shows that it should also contain the putative binding site. Being part of a tRNA synthetases, the insertion domain is likely to be involved in oligonucleotide binding, with possible roles in recognition/discriminati on or editing of prolyl-tRNA. By analogy, YbaK may also play a role in nucl eotide or oligonucleotide binding, the nature of which is yet to be determi ned. (C) 2000 Wiley-Liss, Inc.