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Enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prFMN dependent decarboxylase

The UbiD enzyme plays an important role in bacterial ubiquinone (coenzyme Q) biosynthesis. It belongs to a family of reversible decarboxylases that interconvert propenoic or aromatic acids with the corresponding alkenes or aromatic compounds using a prenylated flavin (prFMN) cofactor. This cofactor...

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Autores principales: Bailey, Samuel S., Payne, Karl A. P., Saaret, Annica, Marshall, Stephen A., Gostimskaya, Irina, Kosov, Iaroslav, Fisher, Karl, Hay, Sam, Leys, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817360/
https://www.ncbi.nlm.nih.gov/pubmed/31527849
http://dx.doi.org/10.1038/s41557-019-0324-8
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author Bailey, Samuel S.
Payne, Karl A. P.
Saaret, Annica
Marshall, Stephen A.
Gostimskaya, Irina
Kosov, Iaroslav
Fisher, Karl
Hay, Sam
Leys, David
author_facet Bailey, Samuel S.
Payne, Karl A. P.
Saaret, Annica
Marshall, Stephen A.
Gostimskaya, Irina
Kosov, Iaroslav
Fisher, Karl
Hay, Sam
Leys, David
author_sort Bailey, Samuel S.
collection PubMed
description The UbiD enzyme plays an important role in bacterial ubiquinone (coenzyme Q) biosynthesis. It belongs to a family of reversible decarboxylases that interconvert propenoic or aromatic acids with the corresponding alkenes or aromatic compounds using a prenylated flavin (prFMN) cofactor. This cofactor is suggested to support (de)carboxylation through a reversible 1,3-dipolar cycloaddition process. Here we report an atomic-level description of the reaction of the UbiD related ferulic acid decarboxylase with substituted propenoic and propiolic acids (data ranging from 1.01 to 1.39 Å). The enzyme is only able to couple (de)carboxylation of cinnamic acid-type compounds to reversible 1,3-dipolar cycloaddition, while formation of dead-end prFMN cycloadducts occurs with distinct propenoic and propiolic acids. The active site imposes considerable strain on covalent intermediates formed with cinnamic and phenylpropiolic acids. Strain reduction through mutagenesis negatively affects catalytic rates with cinnamic acid, indicating a direct link between enzyme-induced strain and catalysis that is supported by computational studies.
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spelling pubmed-68173602020-03-16 Enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prFMN dependent decarboxylase Bailey, Samuel S. Payne, Karl A. P. Saaret, Annica Marshall, Stephen A. Gostimskaya, Irina Kosov, Iaroslav Fisher, Karl Hay, Sam Leys, David Nat Chem Article The UbiD enzyme plays an important role in bacterial ubiquinone (coenzyme Q) biosynthesis. It belongs to a family of reversible decarboxylases that interconvert propenoic or aromatic acids with the corresponding alkenes or aromatic compounds using a prenylated flavin (prFMN) cofactor. This cofactor is suggested to support (de)carboxylation through a reversible 1,3-dipolar cycloaddition process. Here we report an atomic-level description of the reaction of the UbiD related ferulic acid decarboxylase with substituted propenoic and propiolic acids (data ranging from 1.01 to 1.39 Å). The enzyme is only able to couple (de)carboxylation of cinnamic acid-type compounds to reversible 1,3-dipolar cycloaddition, while formation of dead-end prFMN cycloadducts occurs with distinct propenoic and propiolic acids. The active site imposes considerable strain on covalent intermediates formed with cinnamic and phenylpropiolic acids. Strain reduction through mutagenesis negatively affects catalytic rates with cinnamic acid, indicating a direct link between enzyme-induced strain and catalysis that is supported by computational studies. 2019-11-01 2019-09-16 /pmc/articles/PMC6817360/ /pubmed/31527849 http://dx.doi.org/10.1038/s41557-019-0324-8 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Bailey, Samuel S.
Payne, Karl A. P.
Saaret, Annica
Marshall, Stephen A.
Gostimskaya, Irina
Kosov, Iaroslav
Fisher, Karl
Hay, Sam
Leys, David
Enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prFMN dependent decarboxylase
title Enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prFMN dependent decarboxylase
title_full Enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prFMN dependent decarboxylase
title_fullStr Enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prFMN dependent decarboxylase
title_full_unstemmed Enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prFMN dependent decarboxylase
title_short Enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prFMN dependent decarboxylase
title_sort enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prfmn dependent decarboxylase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817360/
https://www.ncbi.nlm.nih.gov/pubmed/31527849
http://dx.doi.org/10.1038/s41557-019-0324-8
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