| Structural highlights
Function
[HMO_AMYOR] Catalyzes the oxidation of p-hydroxymandelate to p-hydroxybenzoylformate in the biosynthesis of L-(4-hydroxyphenyl)glycine and L-(3,5-dihydroxyphenyl)glycine, 2 non-proteinogenic amino acids occurring in the vancomycin group of antibiotics.[1] [2]
Publication Abstract from PubMed
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.
Biochemical and structural explorations of alpha-hydroxyacid oxidases reveal a four-electron oxidative decarboxylation reaction.,Yeh HW, Lin KH, Lyu SY, Li YS, Huang CM, Wang YL, Shih HW, Hsu NS, Wu CJ, Li TL Acta Crystallogr D Struct Biol. 2019 Aug 1;75(Pt 8):733-742. doi:, 10.1107/S2059798319009574. Epub 2019 Jul 30. PMID:31373572[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hubbard BK, Thomas MG, Walsh CT. Biosynthesis of L-p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics. Chem Biol. 2000 Dec;7(12):931-42. PMID:11137816
- ↑ Li TL, Choroba OW, Charles EH, Sandercock AM, Williams DH, Spencer JB. Characterisation of a hydroxymandelate oxidase involved in the biosynthesis of two unusual amino acids occurring in the vancomycin group of antibiotics. Chem Commun (Camb). 2001 Sep 21;(18):1752-3. PMID:12240298
- ↑ Yeh HW, Lin KH, Lyu SY, Li YS, Huang CM, Wang YL, Shih HW, Hsu NS, Wu CJ, Li TL. Biochemical and structural explorations of alpha-hydroxyacid oxidases reveal a four-electron oxidative decarboxylation reaction. Acta Crystallogr D Struct Biol. 2019 Aug 1;75(Pt 8):733-742. doi:, 10.1107/S2059798319009574. Epub 2019 Jul 30. PMID:31373572 doi:http://dx.doi.org/10.1107/S2059798319009574
|
