UbiD domain dynamics underpins aromatic decarboxylation
| Autor: | Karl A. P. Payne, Gabriel R. Titchiner, David Leys, Sam Hay, Colin Levy, Karl Fisher, Stephen A Marshall |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Carboxy-Lyases Flavin Mononucleotide Stereochemistry Decarboxylation Science Allosteric regulation General Physics and Astronomy Article General Biochemistry Genetics and Molecular Biology Substrate Specificity Enzyme catalysis Structure-Activity Relationship Bacterial Proteins Protein Domains Catalytic Domain X-ray crystallography Multidisciplinary Aromatic acid Cycloaddition Reaction biology Viscosity Chemistry Active site Substrate (chemistry) General Chemistry Cycloaddition Enzymes Oxygen Kinetics Protein Subunits Carboxylation Enzyme mechanisms Biocatalysis Solvents biology.protein |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The widespread UbiD enzyme family utilises the prFMN cofactor to achieve reversible decarboxylation of acrylic and (hetero)aromatic compounds. The reaction with acrylic compounds based on reversible 1,3-dipolar cycloaddition between substrate and prFMN occurs within the confines of the active site. In contrast, during aromatic acid decarboxylation, substantial rearrangement of the substrate aromatic moiety associated with covalent catalysis presents a molecular dynamic challenge. Here we determine the crystal structures of the multi-subunit vanillic acid decarboxylase VdcCD. We demonstrate that the small VdcD subunit acts as an allosteric activator of the UbiD-like VdcC. Comparison of distinct VdcCD structures reveals domain motion of the prFMN-binding domain directly affects active site architecture. Docking of substrate and prFMN-adduct species reveals active site reorganisation coupled to domain motion supports rearrangement of the substrate aromatic moiety. Together with kinetic solvent viscosity effects, this establishes prFMN covalent catalysis of aromatic (de)carboxylation is afforded by UbiD dynamics. Understanding the structure and dynamics of enzymes is important for a number of applications. Here, the authors report on the crystal structure of vanillic acid decarboxylase, and show how the dynamics of the UbiD superfamily enzymes relate to the covalent catalysis of aromatic (de)carboxylation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink