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Methylerythritol Phosphate Pathway: Enzymatic Evidence for a Rotation in the LytB/IspH-Catalyzed Reaction.
Chemistry. 2020 Jan 22; 26(5):1032-1036.C

Abstract

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, the synthesis of (S)-[4-2 H1 ]HMBPP and (R)-[4-2 H1 ]HMBPP is reported together with 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)-[4-2 H1 ]HMBPP was converted into [4-2 H1 ]DMAPP and (E)-[4-2 H1 ]IPP, whereas (R)-[4-2 H1 ]HMBPP yielded [4-2 H1 ]DMAPP and (Z)-[4-2 H1 ]IPP, hence providing the direct enzymatic evidence that the mechanism catalyzed by IspH/LytB involves a rotation of the CH2 OH group of the substrate to display it away from the [4Fe-4S].

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Publisher Full Text (DOI)

Authors+Show Affiliations

Chaignon P
Equipe Chimie Biologique et Applications Thérapeutiques, Institut de Chimie UMR 7177, Université de Strasbourg, CNRS, 4, rue Blaise Pascal, 67070, Strasbourg, France.
Petit BE
Equipe Chimie Biologique et Applications Thérapeutiques, Institut de Chimie UMR 7177, Université de Strasbourg, CNRS, 4, rue Blaise Pascal, 67070, Strasbourg, France.
Vincent B
Service de R.M.N., Fédération de Chimie Le Bel FR2010, Université de Strasbourg, CNRS, 1, rue Blaise Pascal, 67008, Strasbourg, France.
Allouche L
Service de R.M.N., Fédération de Chimie Le Bel FR2010, Université de Strasbourg, CNRS, 1, rue Blaise Pascal, 67008, Strasbourg, France.
Seemann M
Equipe Chimie Biologique et Applications Thérapeutiques, Institut de Chimie UMR 7177, Université de Strasbourg, CNRS, 4, rue Blaise Pascal, 67070, Strasbourg, France.

MeSH

BiocatalysisEscherichia coliEscherichia coli ProteinsOrganophosphatesOxidation-ReductionOxidoreductasesPhosphatesSubstrate SpecificityTerpenes

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31756006

Citation

Chaignon, Philippe, et al. "Methylerythritol Phosphate Pathway: Enzymatic Evidence for a Rotation in the LytB/IspH-Catalyzed Reaction." Chemistry (Weinheim an Der Bergstrasse, Germany), vol. 26, no. 5, 2020, pp. 1032-1036.
Chaignon P, Petit BE, Vincent B, et al. Methylerythritol Phosphate Pathway: Enzymatic Evidence for a Rotation in the LytB/IspH-Catalyzed Reaction. Chemistry. 2020;26(5):1032-1036.
Chaignon, P., Petit, B. E., Vincent, B., Allouche, L., & Seemann, M. (2020). Methylerythritol Phosphate Pathway: Enzymatic Evidence for a Rotation in the LytB/IspH-Catalyzed Reaction. Chemistry (Weinheim an Der Bergstrasse, Germany), 26(5), 1032-1036. https://doi.org/10.1002/chem.201904676
Chaignon P, et al. Methylerythritol Phosphate Pathway: Enzymatic Evidence for a Rotation in the LytB/IspH-Catalyzed Reaction. Chemistry. 2020 Jan 22;26(5):1032-1036. PubMed PMID: 31756006.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylerythritol Phosphate Pathway: Enzymatic Evidence for a Rotation in the LytB/IspH-Catalyzed Reaction. AU - Chaignon,Philippe, AU - Petit,Benoît Eric, AU - Vincent,Bruno, AU - Allouche,Lionel, AU - Seemann,Myriam, Y1 - 2020/01/16/ PY - 2019/10/11/received PY - 2019/11/23/pubmed PY - 2020/2/12/medline PY - 2019/11/23/entrez KW - IspH/LytB KW - [4Fe-4S] cluster KW - enzyme catalysis KW - metalloenzymes KW - methylerythritol phosphate pathway SP - 1032 EP - 1036 JF - Chemistry (Weinheim an der Bergstrasse, Germany) JO - Chemistry VL - 26 IS - 5 N2 - 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, the synthesis of (S)-[4-2 H1 ]HMBPP and (R)-[4-2 H1 ]HMBPP is reported together with 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)-[4-2 H1 ]HMBPP was converted into [4-2 H1 ]DMAPP and (E)-[4-2 H1 ]IPP, whereas (R)-[4-2 H1 ]HMBPP yielded [4-2 H1 ]DMAPP and (Z)-[4-2 H1 ]IPP, hence providing the direct enzymatic evidence that the mechanism catalyzed by IspH/LytB involves a rotation of the CH2 OH group of the substrate to display it away from the [4Fe-4S]. SN - 1521-3765 UR - https://www.unboundmedicine.com/medline/citation/31756006/Methylerythritol_Phosphate_Pathway:_Enzymatic_Evidence_for_a_Rotation_in_the_LytB/IspH_Catalyzed_Reaction_ DB - PRIME DP - Unbound Medicine ER -