7JMV

Crystal structure of the pea pathogenicity protein 2 from Madurella mycetomatis complexed with 4-nitrocatechol


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.177 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Crystal structures of non-oxidative decarboxylases reveal a new mechanism of action with a catalytic dyad and structural twists.

Zeug, M.Markovic, N.Iancu, C.V.Tripp, J.Oreb, M.Choe, J.Y.

(2021) Sci Rep 11: 3056-3056

  • DOI: https://doi.org/10.1038/s41598-021-82660-z
  • Primary Citation of Related Structures:  
    6W54, 7JMR, 7JMV, 7KD9

  • PubMed Abstract: 

    Hydroxybenzoic acids, like gallic acid and protocatechuic acid, are highly abundant natural compounds. In biotechnology, they serve as critical precursors for various molecules in heterologous production pathways, but a major bottleneck is these acids' non-oxidative decarboxylation to hydroxybenzenes. Optimizing this step by pathway and enzyme engineering is tedious, partly because of the complicating cofactor dependencies of the commonly used prFMN-dependent decarboxylases. Here, we report the crystal structures (1.5-1.9 Å) of two homologous fungal decarboxylases, AGDC1 from Arxula adenivorans, and PPP2 from Madurella mycetomatis. Remarkably, both decarboxylases are cofactor independent and are superior to prFMN-dependent decarboxylases when heterologously expressed in Saccharomyces cerevisiae. The organization of their active site, together with mutational studies, suggests a novel decarboxylation mechanism that combines acid-base catalysis and transition state stabilization. Both enzymes are trimers, with a central potassium binding site. In each monomer, potassium introduces a local twist in a β-sheet close to the active site, which primes the critical H86-D40 dyad for catalysis. A conserved pair of tryptophans, W35 and W61, acts like a clamp that destabilizes the substrate by twisting its carboxyl group relative to the phenol moiety. These findings reveal AGDC1 and PPP2 as founding members of a so far overlooked group of cofactor independent decarboxylases and suggest strategies to engineer their unique chemistry for a wide variety of biotechnological applications.


  • Organizational Affiliation

    Department of Chemistry, Biochemistry, and Pharmacy, Goethe University Frankfurt, Frankfurt am Main, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Pea pathogenicity protein 2243Madurella mycetomatisMutation(s): 0 
Gene Names: MMYC01_201259MMYC01_203104
UniProt
Find proteins for A0A175WC91 (Madurella mycetomatis)
Explore A0A175WC91 
Go to UniProtKB:  A0A175WC91
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A175WC91
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.57 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.177 
  • Space Group: P 3 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 98.74α = 90
b = 98.74β = 90
c = 62.287γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2021-02-17
    Type: Initial release
  • Version 1.1: 2023-10-18
    Changes: Data collection, Database references, Refinement description