RCSB PDB - 4ZA4: Structure of A. niger Fdc1 with the prenylated-flavin cofactor in the iminium form.

 4ZA4

Structure of A. niger Fdc1 with the prenylated-flavin cofactor in the iminium form.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.22 Å
  • R-Value Free: 0.161 
  • R-Value Work: 0.146 
  • R-Value Observed: 0.147 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 4LUClick on this verticalbar to view details

This is version 1.3 of the entry. See complete history


Literature

New cofactor supports alpha , beta-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition.

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

(2015) Nature 522: 502-506

  • DOI: https://doi.org/10.1038/nature14560
  • Primary Citation of Related Structures:  
    4ZA4, 4ZA5, 4ZA7, 4ZA8, 4ZA9, 4ZAA, 4ZAB, 4ZAC, 4ZAD

  • PubMed 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.


  • Organizational Affiliation

    Centre for Synthetic Biology of Fine and Speciality Chemicals, Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fdc1508Aspergillus niger CBS 513.88Mutation(s): 0 
Gene Names: An03g06590
EC: 4.1.1.61 (PDB Primary Data), 4.1.1.102 (UniProt)
UniProt
Find proteins for A2QHE5 (Aspergillus niger (strain ATCC MYA-4892 / CBS 513.88 / FGSC A1513))
Explore A2QHE5 
Go to UniProtKB:  A2QHE5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA2QHE5
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.22 Å
  • R-Value Free: 0.161 
  • R-Value Work: 0.146 
  • R-Value Observed: 0.147 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 95.99α = 90
b = 63.93β = 90
c = 87.63γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
xia2data reduction
xia2data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 4LUClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Biotechnology and Biological Sciences Research CouncilUnited Kingdom--

Revision History  (Full details and data files)

  • Version 1.0: 2015-06-17
    Type: Initial release
  • Version 1.1: 2015-07-01
    Changes: Database references
  • Version 1.2: 2017-08-30
    Changes: Author supporting evidence
  • Version 1.3: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Structure summary