UbiD domain dynamics underpins aromatic decarboxylation

Marshall, Stephen A, Payne, Karl AP ORCID: 0000-0002-6331-6374, Fisher, Karl, Titchiner, Gabriel R, Levy, Colin, Hay, Sam and Leys, David (2021) UbiD domain dynamics underpins aromatic decarboxylation. NATURE COMMUNICATIONS, 12 (1). 5065-.

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Official URL: http://dx.doi.org/10.1038/s41467-021-25278-z

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Oxygen, Flavin Mononucleotide, Carboxy-Lyases, Bacterial Proteins, Protein Subunits, Solvents, Catalytic Domain, Structure-Activity Relationship, Substrate Specificity, Decarboxylation, Kinetics, Viscosity, Models, Molecular, Biocatalysis, Cycloaddition Reaction, Protein Domains
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	18 Jan 2022 09:34
Last Modified:	18 Jan 2023 21:15
DOI:	10.1038/s41467-021-25278-z
Open Access URL:	https://doi.org/10.1038/s41467-021-25278-z
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3147092