Enzymatic control of cycloadduct conformation ensures reversible 1,3-dipolar cycloaddition in a prFMN-dependent decarboxylase
| Autor: | David Leys, Annica Saaret, Karl A. P. Payne, Samuel S. Bailey, Iaroslav Kosov, Stephen A. Marshall, Sam Hay, Irina Gostimskaya, Karl Fisher |
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| Jazyk: | angličtina |
| Předmět: |
Models
Molecular Stereochemistry Carboxy-Lyases General Chemical Engineering Molecular Conformation Flavin mononucleotide 010402 general chemistry 01 natural sciences Reversible reaction Cinnamic acid Cofactor Article chemistry.chemical_compound Density Functional Theory biology Cycloaddition Reaction 010405 organic chemistry Chemistry Active site General Chemistry Cycloaddition 0104 chemical sciences Carboxylation Alkynes 1 3-Dipolar cycloaddition biology.protein Biocatalysis Propionates |
| Zdroj: | Nature Chemistry Bailey, S, Payne, K, Saaret, A, Marshall, S, Gostimskaya, I, Kosov, I, Fisher, K, Hay, S & Leys, D 2019, ' Enzymatic control of cycloadduct conformation ensures reversible 1,3 dipolar cycloaddition in a prFMN dependent decarboxylase ', Nature Chemistry, vol. 11, pp. 1049-1057 . https://doi.org/10.1038/s41557-019-0324-8 Nature chemistry |
| ISSN: | 1755-4349 1755-4330 |
| DOI: | 10.1038/s41557-019-0324-8 |
| Popis: | 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 mononucleotide 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 1.01–1.39 A). The enzyme is only able to couple (de)carboxylation of cinnamic acid-type compounds to reversible 1,3-dipolar cycloaddition, while the formation of dead-end prenylated flavin mononucleotide 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. The UbiD family of reversible decarboxylases interconvert propenoic or aromatic acids with the corresponding alkenes or aromatic compounds, using a transient 1,3-dipolar cycloaddition between the substrate and the prenylated flavin mononucleotide cofactor. Atomic-resolution crystallography shows targeted destabilization of the intermediate covalent adducts, allowing the enzyme to harness 1,3-dipolar cycloaddition as a readily reversible reaction. |
| Databáze: | OpenAIRE |
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