7ABO

Structure of the N318H variant of the reversible pyrrole-2-carboxylic acid decarboxylase PA0254/HudA in complex with FMN

7ABO の概要

• エントリーDOI: 10.2210/pdb7abo/pdb
• 分子名称: UbiD-like decarboxylase, FLAVIN MONONUCLEOTIDE, MANGANESE (II) ION, ... (5 entities in total)
• 機能のキーワード: prfmn, decarboxylase, ubid, pyrrole, pyrrole-2-carboxylic acid, ligase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 221942.14

構造登録者

Leys, D.,Marshall, S.A. (登録日: 2020-09-08, 公開日: 2021-04-07, 最終更新日: 2024-01-31)

主引用文献

Payne, K.A.P.,Marshall, S.A.,Fisher, K.,Rigby, S.E.J.,Cliff, M.J.,Spiess, R.,Cannas, D.M.,Larrosa, I.,Hay, S.,Leys, D.
Structure and Mechanism of Pseudomonas aeruginosa PA0254/HudA, a prFMN-Dependent Pyrrole-2-carboxylic Acid Decarboxylase Linked to Virulence.
Acs Catalysis, 11:2865-2878, 2021

PubMed Abstract: The UbiD family of reversible (de)carboxylases depends on the recently discovered prenylated-FMN (prFMN) cofactor for activity. The model enzyme ferulic acid decarboxylase (Fdc1) decarboxylates unsaturated aliphatic acids via a reversible 1,3-cycloaddition process. Protein engineering has extended the Fdc1 substrate range to include (hetero)aromatic acids, although catalytic rates remain poor. This raises the question how efficient decarboxylation of (hetero)aromatic acids is achieved by other UbiD family members. Here, we show that the virulence attenuation factor PA0254HudA is a pyrrole-2-carboxylic acid decarboxylase. The crystal structure of the enzyme in the presence of the reversible inhibitor imidazole reveals a covalent prFMNimidazole adduct is formed. Substrate screening reveals HudA and selected active site variants can accept a modest range of heteroaromatic compounds, including thiophene-2-carboxylic acid. Together with computational studies, our data suggests prFMN covalent catalysis occurs via electrophilic aromatic substitution and links HudA activity with the inhibitory effects of pyrrole-2-carboxylic acid on quorum sensing.

PubMed: 33763291
DOI: 10.1021/acscatal.0c05042

実験手法

X-RAY DIFFRACTION (1.95 Å)