6evd
Structure of R173A A. niger Fdc1 with prFMN in the hydroxylated form
Structural highlights
Function[FDC1_ASPNC] Catalyzes the reversible decarboxylation of aromatic carboxylic acids like ferulic acid, p-coumaric acid or cinnamic acid, producing the corresponding vinyl derivatives 4-vinylphenol, 4-vinylguaiacol, and styrene, respectively, which play the role of aroma metabolites.[HAMAP-Rule:MF_03196][1] Publication Abstract from PubMedThe UbiD family of reversible decarboxylases act on aromatic, heteroaromatic, and unsaturated aliphatic acids and utilize a prenylated flavin mononucleotide (prFMN) as cofactor, bound adjacent to a conserved Glu-ArgGlu/Asp ionic network in the enzyme's active site. It is proposed that UbiD activation requires oxidative maturation of the cofactor, for which two distinct isomers, prFMN(ketimine) and prFMN(iminium) have been observed. It also has been suggested that only the prFMN(iminium) form is relevant to catalysis, which requires transient cycloaddition between substrate and cofactor. Using Aspergillus niger Fdc1 as a model system, we reveal isomerization of prFMN(iminium) to prFMN(ketimine) is a light-dependent process that is largely independent of the Glu277-Arg173-Glu282 network and accompanied by irreversible loss of activity. On the other hand, efficient catalysis was highly dependent on an intact Glu-Ar-Glu network, as only Glu to Asp substitutions retain activity. Surprisingly, oxidative maturation to form the prFMN(iminium) species is severely affected only for the R173A variant. In summary, the unusual irreversible isomerization of prFMN is light dependent and likely proceeds via high-energy intermediates, but is independent of the Glu-Arg-Glu network. Our results from mutagenesis, crystallographic, spectroscopic and kinetic experiments indicate a clear role for the Glu-Arg-Glu network in both catalysis and oxidative maturation. The role of conserved residues in Fdc decarboxylase in prenylated flavin mononucleotide oxidative maturation, cofactor isomerisation and catalysis.,Bailey SS, Payne KAP, Fisher K, Marshall SA, Cliff MJ, Spiess R, Parker DA, Rigby SE, Leys D J Biol Chem. 2017 Dec 19. pii: RA117.000881. doi: 10.1074/jbc.RA117.000881. PMID:29259125[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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