The PHBH fold: not only flavoenzymes.
p-Hydroxybenzoate hydroxylase, D-amino acid oxidase, cholesterol oxidase and glucose oxidase form a family of structurally related flavoenzymes. Comparison of their three-dimensional structures reveal how the same FAD-binding scaffold has been employed to implement diverse active-site architectures, suited for different types of catalytic reactions. The substrate binding mode differs in each of these enzymes, with the catalytically relevant residues not located on homologous positions. A common feature is provided by the ability of these enzyme to bury their substrates beneath the protein surface. In D-amino acid oxidase and cholesterol oxidase, a loop forms a 'lid' controlling the active site accessibility, whereas in p-hydroxybenzoate hydroxylase is the flavin itself, which swings out to allow substrate binding. The crystallographic analysis has revealed that the GTP-dissociation inhibitor of RAB GTPases has a folding topology remarkably similar to p-hydroxybenzoate hydroxylase. This finding highlights the versatile nature of this folding topology, which in addition to flavin-dependent catalysis, is suited for diverse functions, such as the regulation of GTPases.
Mattevi
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Department of Genetics and Microbiology, University of Pavia, Italy. mattevi@ipvgen.unipv.it
D015109:4-Hydroxybenzoate-3-Monooxygenase / Q000737:chemistry*; D001665:Binding Sites; D005075:Biological Evolution; D002384:Catalysis; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding
D015109:4-Hydroxybenzoate-3-Monooxygenase