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Structure-based functional annotation: yeast ymr099c codes for a D-hexose-6-phosphate mutarotase.
Marc Graille1, Jean-Pierre Baltaze, Nicolas Leulliot
1Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, Université Paris-Sud, IFR115, CNRS UMR8619, F-91405 Orsay Cedex, France.
The Journal of Biological Chemistry
|July 22, 2006
Summary
Structural genomics identified Saccharomyces cerevisiae YMR099cp as a hexose-6-phosphate mutarotase. This protein, previously of unknown function, plays a key metabolic role, confirmed by crystal structures.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Many characterized enzymatic functions lack associated protein sequences.
- Assigning protein sequences to biochemical functions is a significant challenge in bioinformatics.
- Structural genomics offers a promising approach to address this gap.
Purpose of the Study:
- To determine the function of the Saccharomyces cerevisiae protein YMR099cp.
- To utilize structural information to assign protein sequences to enzymatic activities.
- To investigate the metabolic role of YMR099cp.
Main Methods:
- X-ray crystallography to determine the 3D structure of YMR099cp.
- Structural comparison with known enzymes like galactose mutarotase.
- Biochemical assays to test enzymatic activity and substrate specificity.
- Solving crystal structures of enzyme-substrate complexes.
Main Results:
- The crystal structure of YMR099cp was determined, revealing a fold similar to galactose mutarotase.
- A sulfate ion in the active site mimicked the hexose 6-phosphate substrate.
- YMR099cp was identified as a hexose-6-phosphate mutarotase with broad substrate specificity.
- High-resolution structures of enzyme-substrate complexes confirmed the functional assignment.
Conclusions:
- Structural genomics successfully assigned the orphan EC activity of hexose-phosphate mutarotase to YMR099cp.
- The study highlights the crucial role of structural information in functional annotation of proteins.
- The metabolic significance of hexose-6-phosphate mutarotase activity is discussed.