Structure of a yeast hypothetical protein selected by a structural genomics approach.
Yeast hypothetical protein YBL036C (SWISS-PROT P38197), initially thought to be a member of an 11-protein family, was selected for crystal structure determination since no structural or functional information was available. The structure has been determined independently by MIR and MAD methods to 2.0 A resolution. The MAD structure was determined largely through automated model building. The protein folds as a TIM barrel beginning with a long N-terminal helix, in contrast to the classic triose phosphate isomerase (TIM) structure, which begins with a beta-strand. A cofactor, pyridoxal 5'-phosphate, is covalently bound near the C-terminal end of the barrel, the usual active site in TIM-barrel folds. A single-domain monomeric molecule, this yeast protein resembles the N-terminal domain of alanine racemase or ornithine decarboxylase, both of which are two-domain dimeric proteins. The yeast protein has been shown to have amino-acid racemase activity. Although selected as a member of a protein family having no obvious relationship to proteins of known structure, the protein fold turned out to be a well known and widely distributed fold. This points to the need for a more comprehensive base of structural information and better structure-modeling tools before the goal of structure prediction from amino-acid sequences can be realised. In this case, similarity to a known structure allowed inferences to be made about the structure and function of a widely distributed protein family.
Eswaramoorthy
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Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Gerchman
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Graziano
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Kycia
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Studier
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Swaminathan
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D000411:Alanine Racemase / Q000737:chemistry; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray / Q000379:methods; D030562:Databases, Protein; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D023281:Genomics / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009955:Ornithine Decarboxylase / Q000737:chemistry; D017433:Protein Structure, Secondary; D011732:Pyridoxal Phosphate / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014305:Triose-Phosphate Isomerase / Q000737:chemistry / Q000378:metabolism
D005656:Fungal Proteins; D011732:Pyridoxal Phosphate; D009955:Ornithine Decarboxylase; D000411:Alanine Racemase; D014305:Triose-Phosphate Isomerase