The PHBH fold: Not only flavoenzymes |
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Authors: | Andrea Mattevi |
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Institution: | a Department of Genetics and Microbiology, University of Pavia, via Abbiategrasso 207 27100 Pavia Italy |
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Abstract: | p-Hydroxybenzoate hydroxylase, -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 -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. |
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Keywords: | FAD-dependent catalysis Favoenzyme Folding topology Cavity Divergent evolution |
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