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Article Dans Une Revue Chemistry - A European Journal Année : 2019

Methylerythritol Phosphate Pathway: Enzymatic Evidence for a Rotation in the LytB/IspH Catalyzed Reaction

Résumé

IspH/LytB, an oxygen-sensitive [4Fe-4S] enzyme, catalyzes the last step of the methylerythritol phosphate (MEP) pathway, a target for the development of new antimicrobial agents. This metalloenzyme converts (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Here, we report the synthesis of (S)-[4-2H1]HMBPP and (R)-[4-2H1]HMBPP, and a detailed NMR analysis of the products formed after their respective incubation with E. coli IspH/LytB in the presence of the biological reduction system used by E.coli to reduce the [4Fe-4S] center. (S)-[4-2H1]HMBPP was converted into [4-2H1]DMAPP and (E)-[4-2H1]IPP whereas (R)-[4-2H1]HMBPP yielded [4-2H1]DMAPP and (Z)-[4-2H1]IPP, hence providing the direct enzymatic evidence that the mechanism catalyzed by IspH/LytB involves a rotation of the CH2OH group of the substrate to display it away from the [4Fe-4S].
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Dates et versions

hal-02407672 , version 1 (20-11-2020)

Identifiants

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Philippe Chaignon, Benoit Eric Petit, Bruno Vincent, Lionel Allouche, Myriam Seemann. Methylerythritol Phosphate Pathway: Enzymatic Evidence for a Rotation in the LytB/IspH Catalyzed Reaction. Chemistry - A European Journal, 2019, ⟨10.1002/chem.201904676⟩. ⟨hal-02407672⟩
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