PDBsum entry 4zab

Lyase

PDB id: 4zab

Contents

Protein chain

500 a.a.

Ligands

4LU-FZZ

4LW

Metals

_MN

__K ×2

Waters ×485

PDB id:

4zab

Name:

Lyase

Title:

Structure of a. Niger fdc1 in complex with alpha-fluoro cinnamic acid

Structure:

A niger fdc1. Chain: a. Engineered: yes

Source:

Aspergillus niger (strain cbs 513.88 / fgsc a1513). Organism_taxid: 425011. Strain: cbs 513.88 / fgsc a1513. Gene: an03g06590. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.16Å R-factor: 0.147 R-free: 0.154

Authors:

K.A.P.Payne,D.Leys

Key ref:

K.A.Payne et al. (2015). New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition. Nature, 522, 497-501. PubMed id: 26083754 DOI: 10.1038/nature14560

Date:

13-Apr-15 Release date: 17-Jun-15

Protein chain

A2QHE5  (FDC1_ASPNC) -  Ferulic acid decarboxylase 1 from Aspergillus niger (strain ATCC MYA-4892 / CBS 513.88 / FGSC A1513)

Seq: 500 a.a.

Struc: 500 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.4.1.1.102 - phenacrylate decarboxylase.
• Reaction:
  1. (E)-4-coumarate + H⁺ = 4-vinylphenol + CO2
  2. (E)-cinnamate + H⁺ = styrene + CO2
  3. (E)-ferulate + H⁺ = 2-methoxy-4-vinylphenol + CO2

(E)-4-coumarate + H(+) = 4-vinylphenol (Bound ligand (Het Group name = 4LW) matches with 75.00% similarity) + CO2

(E)-cinnamate (Bound ligand (Het Group name = 4LW) matches with 91.67% similarity) + H(+) = styrene + CO2

• Cofactor: Prenyl-FMNH(2)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/nature14560

Nature 522:497-501 (2015)

PubMed id: 26083754

New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition.

K.A.Payne, M.D.White, K.Fisher, B.Khara, S.S.Bailey, D.Parker, N.J.Rattray, D.K.Trivedi, R.Goodacre, R.Beveridge, P.Barran, S.E.Rigby, N.S.Scrutton, S.Hay, D.Leys.

ABSTRACT

The bacterial ubiD and ubiX or the homologous fungal fdc1 and pad1 genes have been implicated in the non-oxidative reversible decarboxylation of aromatic substrates, and play a pivotal role in bacterial ubiquinone (also known as coenzyme Q) biosynthesis or microbial biodegradation of aromatic compounds, respectively. Despite biochemical studies on individual gene products, the composition and cofactor requirement of the enzyme responsible for in vivo decarboxylase activity remained unclear. Here we show that Fdc1 is solely responsible for the reversible decarboxylase activity, and that it requires a new type of cofactor: a prenylated flavin synthesized by the associated UbiX/Pad1. Atomic resolution crystal structures reveal that two distinct isomers of the oxidized cofactor can be observed, an isoalloxazine N5-iminium adduct and a N5 secondary ketimine species with markedly altered ring structure, both having azomethine ylide character. Substrate binding positions the dipolarophile enoic acid group directly above the azomethine ylide group. The structure of a covalent inhibitor-cofactor adduct suggests that 1,3-dipolar cycloaddition chemistry supports reversible decarboxylation in these enzymes. Although 1,3-dipolar cycloaddition is commonly used in organic chemistry, we propose that this presents the first example, to our knowledge, of an enzymatic 1,3-dipolar cycloaddition reaction. Our model for Fdc1/UbiD catalysis offers new routes in alkene hydrocarbon production or aryl (de)carboxylation.