Evolution of the arginase fold and functional diversity
D P Dowling1, L Di Costanzo, H A Gennadios
1Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
Cellular and Molecular Life Sciences : CMLS
|March 25, 2008
Summary
Protein structural superfamilies reveal evolutionary links between enzymes like arginase and histone deacetylases. This highlights how conserved protein folds, not just sequence, uncover distant evolutionary relationships.
Area of Science:
- Biochemistry
- Structural Biology
- Evolutionary Biology
Background:
- Protein Data Bank (PDB) contains numerous protein structures.
- Sequence identity can diverge rapidly during protein evolution.
- Conserved protein folds can indicate deeper evolutionary relationships.
Purpose of the Study:
- To review the unique alpha/beta fold found in rat liver arginase.
- To explore the evolutionary relationship between this fold and histone deacetylases and acetylpolyamine amidohydrolases.
- To understand how fold features influence metal ion specificity.
Main Methods:
- Structural comparison of protein folds.
- Analysis of amino acid sequence conservation.
- Examination of metalloenzyme structures.
Main Results:
- A unique alpha/beta fold, characterized by a parallel eight-stranded beta-sheet and surrounding helices, was identified.
- This fold is shared with zinc- and/or iron-requiring enzymes, including histone deacetylases and acetylpolyamine amidohydrolases.
- Key fold features dictate divergent metal ion specificity and stoichiometry.
Conclusions:
- Conserved protein folds are crucial for identifying novel structural superfamilies.
- Unanticipated evolutionary relationships exist between enzymes with similar folds but low sequence identity.
- The alpha/beta fold's structural characteristics are central to the functional diversity of these metalloenzymes.
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