التفاصيل البيبلوغرافية
| العنوان: |
The flavin mononucleotide cofactor in α‐hydroxyacid oxidases exerts its electrophilic/nucleophilic duality in control of the substrate‐oxidation level. |
| المؤلفون: |
Lyu, Syue-Yi, Lin, Kuan-Hung, Yeh, Hsien-Wei, Li, Yi-Shan, Huang, Chun-Man, Wang, Yung-Lin, Shih, Hao-Wei, Hsu, Ning-Shian, Wu, Chang-Jer, Li, Tsung-Lin |
| المصدر: |
Acta Crystallographica: Section D, Structural Biology; Oct2019, Vol. 75 Issue 10, p918-929, 12p |
| مصطلحات موضوعية: |
FLAVIN mononucleotide, OXIDASES, HYDROGEN peroxide, DECARBOXYLATION, CARBANIONS, NUCLEOPHILIC reactions |
| مستخلص: |
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 α‐ketoacid, forming an N5‐acyl‐FMNred dead‐end adduct. In four‐electron oxidation, an intramolecular disproportionation reaction via an N5‐alkanol‐FMNred C′α carbanion intermediate may account for the ThDP/PLP/NADPH‐independent oxidative decarboxylation reaction. A synthetic 5‐deaza‐FMNox cofactor in combination with an α‐hydroxyamide or α‐ketoamide biochemically and structurally supports the proposed mechanism. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
