title: Crystal structure of YbaK protein from Haemophilus influenzae (HI1434) at 1.8 A resolution: functional implications.
abstract: Structural genomics of proteins of unknown function most straightforwardly assists with assignment of biochemical activity when the new structure resembles that of proteins whose functions are known. When a new fold is revealed, the universe of known folds is enriched, and once the function is determined by other means, novel structure-function relationships are established. The previously unannotated protein HI1434 from H. influenzae provides a hybrid example of these two paradigms. It is a member of a microbial protein family, labeled in SwissProt as YbaK and ebsC. The crystal structure at 1.8 A 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 proteins. However, a crevice that may accommodate a small ligand is evident. The 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 homology to an insertion domain in prolyl-tRNA synthetases (proRS) from prokaryote, a domain whose function is unknown. A HI1434-based model of the insertion 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/discrimination or editing of prolyl-tRNA. By analogy, YbaK may also play a role in nucleotide or oligonucleotide binding, the nature of which is yet to be determined.
authors.affiliation: Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, MD 20850, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Huang
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Banerjei
authors.forename: K E
authors.initials: KE
authors.lastname: Fisher
authors.forename: N V
authors.initials: NV
authors.lastname: Grishin
authors.forename: E
authors.initials: E
authors.lastname: Eisenstein
authors.forename: O
authors.initials: O
authors.lastname: Herzberg
mesh_terms: D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry; D001426:Bacterial Proteins; D019757:Carbon-Oxygen Lyases; D002352:Carrier Proteins / Q000737:chemistry* / Q000302:isolation & purification; D018360:Crystallography, X-Ray; D006193:Haemophilus influenzae / Q000737:chemistry*; D037102:Lectins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D037102:Lectins; D019757:Carbon-Oxygen Lyases; C412282:HI1434 protein, Haemophilus influenzae; D000604:Amino Acyl-tRNA Synthetases; C100134:prolyl T RNA synthetase