Identification of Unknown Protein Function Using Metabolite Cocktail Screening
| Autor: | Kula N. Jha, Igor A. Shumilin, Andrzej Joachimiak, Olga Chertihin, Wladek Minor, Scott A. Lesley, John C. Herr, Marcin Cymborowski |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Protein family Metabolite Racemases and Epimerases Plasma protein binding Crystallography X-Ray Article Protein Structure Secondary Small Molecule Libraries Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein structure Bacterial Proteins Structural Biology Catalytic Domain Animals Thermotoga maritima Molecular Biology Hydro-Lyases 030304 developmental biology ADP Ribose Transferases 0303 health sciences biology Binding protein Hydrogen Bonding Molecular Sequence Annotation Phosphoproteins Ligand (biochemistry) biology.organism_classification Protein Structure Tertiary chemistry Biochemistry Carrier Proteins 030217 neurology & neurosurgery Function (biology) Bacillus subtilis Protein Binding |
| Zdroj: | Structure. 20(10):1715-1725 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2012.07.016 |
| Popis: | SummaryProteins of unknown function comprise a significant fraction of sequenced genomes. Defining the roles of these proteins is vital to understanding cellular processes. Here, we describe a method to determine a protein function based on the identification of its natural ligand(s) by the crystallographic screening of the binding of a metabolite library, followed by a focused search in the metabolic space. The method was applied to two protein families with unknown function, PF01256 and YjeF_N. The PF01256 proteins, represented by YxkO from Bacillus subtilis and the C-terminal domain of Tm0922 from Thermotoga maritima, were shown to catalyze ADP/ATP-dependent NAD(P)H-hydrate dehydratation, a previously described orphan activity. The YjeF_N proteins, represented by mouse apolipoprotein A-I binding protein and the N-terminal domain of Tm0922, were found to interact with an adenosine diphosphoribose-related substrate and likely serve as ADP-ribosyltransferases. Crystallographic screening of metabolites serves as an efficient tool in functional analyses of uncharacterized proteins. |
| Databáze: | OpenAIRE |
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