Biochemical and structural explorations of α-hydroxyacid oxidases reveal a four-electron oxidative decarboxylation reaction.
Acta Crystallogr D Struct Biol
; 75(Pt 8): 733-742, 2019 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-31373572
ABSTRACT
p-Hydroxymandelate oxidase (Hmo) is a flavin mononucleotide (FMN)-dependent enzyme that oxidizes mandelate to benzoylformate. How the FMN-dependent oxidation is executed by Hmo remains unclear at the molecular level. A continuum of snapshots from crystal structures of Hmo and its mutants in complex with physiological/nonphysiological substrates, products and inhibitors provides a rationale for its substrate enantioselectivity/promiscuity, its active-site geometry/reactivity and its direct hydride-transfer mechanism. A single mutant, Y128F, that extends the two-electron oxidation reaction to a four-electron oxidative decarboxylation reaction was unexpectedly observed. Biochemical and structural approaches, including biochemistry, kinetics, stable isotope labeling and X-ray crystallography, were exploited to reach these conclusions and provide additional insights.
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Base de dados:
MEDLINE
Assunto principal:
Oxirredutases do Álcool
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Mononucleotídeo de Flavina
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Ácidos Mandélicos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article