Related Experiment Videos
The PHBH fold: not only flavoenzymes
1Department of Genetics and Microbiology, University of Pavia, Italy. mattevi@ipvgen.unipv.it
Biophysical Chemistry
|April 18, 1998
Summary
Flavoenzymes like p-hydroxybenzoate hydroxylase share a common FAD-binding scaffold but exhibit diverse active sites for varied reactions. This structural motif is also found in GTPase regulators, highlighting its functional versatility.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- p-Hydroxybenzoate hydroxylase, D-amino acid oxidase, cholesterol oxidase, and glucose oxidase are structurally related flavoenzymes.
- These enzymes utilize a conserved FAD-binding scaffold but possess distinct active-site architectures for different catalytic reactions.
Purpose of the Study:
- To compare the three-dimensional structures of related flavoenzymes.
- To understand how a common FAD-binding scaffold supports diverse active-site architectures and functions.
- To explore the functional versatility of a specific protein folding topology.
Main Methods:
- Comparative analysis of three-dimensional structures of flavoenzymes.
- Crystallographic analysis of GTP-dissociation inhibitor of RAB GTPases.
Main Results:
- Flavoenzymes share a common FAD-binding scaffold but differ in substrate binding modes and active-site residue positions.
- A common feature is the burial of substrates beneath the protein surface, with varying mechanisms for active site accessibility.
- The GTP-dissociation inhibitor of RAB GTPases shares a folding topology with p-hydroxybenzoate hydroxylase.
Conclusions:
- The conserved FAD-binding scaffold in flavoenzymes can accommodate diverse active-site designs for varied catalytic functions.
- The identified protein folding topology is versatile, supporting both flavin-dependent catalysis and GTPase regulation.
- Structural insights reveal how enzymes evolve similar scaffolds for functionally distinct roles.