6a1l

Mandelate oxidase mutant-Y128F with 5-deazariboflavin mononucleotide and benzoic acid

spinqualitylabelsall models 6a1l, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6a1l is a 1 chain structure with sequence from Amycolatopsis orientalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: 9O9, BEZ, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed The Y128F single mutant of p-hydroxymandelate oxidase (Hmo) is capable of oxidizing mandelate to benzoate via a four-electron oxidative decarboxylation reaction. When benzoylformate (the product of the first two-electron oxidation) and hydrogen peroxide (an oxidant) were used as substrates the reaction did not proceed, suggesting that free hydrogen peroxide is not the committed oxidant in the second two-electron oxidation. How the flavin mononucleotide (FMN)-dependent four-electron oxidation reaction takes place remains elusive. Structural and biochemical explorations have shed new light on this issue. 15 high-resolution crystal structures of Hmo and its mutants liganded with or without a substrate reveal that oxidized FMN (FMNox) possesses a previously unknown electrophilic/nucleophilic duality. In the Y128F mutant the active-site perturbation ensemble facilitates the polarization of FMNox to a nucleophilic ylide, which is in a position to act on an alpha-ketoacid, forming an N5-acyl-FMNred dead-end adduct. In four-electron oxidation, an intramolecular disproportionation reaction via an N5-alkanol-FMNred C'alpha carbanion intermediate may account for the ThDP/PLP/NADPH-independent oxidative decarboxylation reaction. A synthetic 5-deaza-FMNox cofactor in combination with an alpha-hydroxyamide or alpha-ketoamide biochemically and structurally supports the proposed mechanism. The flavin mononucleotide cofactor in alpha-hydroxyacid oxidases exerts its electrophilic/nucleophilic duality in control of the substrate-oxidation level.,Lyu SY, Lin KH, Yeh HW, Li YS, Huang CM, Wang YL, Shih HW, Hsu NS, Wu CJ, Li TL Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):918-929. doi:, 10.1107/S2059798319011938. Epub 2019 Sep 24. PMID:31588923 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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