5ZCM

Crystal structure of Xylose reductase from Debaryomyces nepalensis in complex with NADP-DTT adduct


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.164 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history


Literature

Crystal structure of yeast xylose reductase in complex with a novel NADP-DTT adduct provides insights into substrate recognition and catalysis.

Paidimuddala, B.Mohapatra, S.B.Gummadi, S.N.Manoj, N.

(2018) FEBS J 285: 4445-4464

  • DOI: https://doi.org/10.1111/febs.14667
  • Primary Citation of Related Structures:  
    5ZCI, 5ZCM

  • PubMed Abstract: 

    Aldose reductases (ARs) belonging to the aldo-keto reductase (AKR) superfamily catalyze the conversion of carbonyl substrates into their respective alcohols. Here we report the crystal structures of the yeast Debaryomyces nepalensis xylose reductase (DnXR, AKR2B10) in the apo form and as a ternary complex with a novel NADP-DTT adduct. Xylose reductase, a key enzyme in the conversion of xylose to xylitol, has several industrial applications. The enzyme displayed the highest catalytic efficiency for l-threose (138 ± 7 mm -1 ·s -1 ) followed by d-erythrose (30 ± 3 mm -1 ·s -1 ). The crystal structure of the complex reveals a covalent linkage between the C4N atom of the nicotinamide ring of the cosubstrate and the S1 sulfur atom of DTT and provides the first structural evidence for a protein mediated NADP-low-molecular-mass thiol adduct. We hypothesize that the formation of the adduct is facilitated by an in-crystallo Michael addition of the DTT thiolate to the specific conformation of bound NADPH in the active site of DnXR. The interactions between DTT, a four-carbon sugar alcohol analog, and the enzyme are representative of a near-cognate product ternary complex and provide significant insights into the structural basis of aldose binding and specificity and the catalytic mechanism of ARs. DATABASE: Structural data are available in the PDB under the accession numbers 5ZCI and 5ZCM.


  • Organizational Affiliation

    Applied and Industrial Microbiology Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aldose reductase341Debaryomyces nepalensisMutation(s): 0 
Gene Names: AR
EC: 1.1.1.21 (PDB Primary Data), 1.1.1.307 (UniProt)
UniProt
Find proteins for A0A0M4HL56 (Debaryomyces nepalensis)
Explore A0A0M4HL56 
Go to UniProtKB:  A0A0M4HL56
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0M4HL56
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.164 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.59α = 90
b = 108.22β = 90
c = 71.82γ = 90
Software Package:
Software NamePurpose
XDSdata reduction
Aimlessdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2018-11-07 
  • Deposition Author(s): Manoj, N.

Revision History  (Full details and data files)

  • Version 1.0: 2018-11-07
    Type: Initial release
  • Version 1.1: 2018-12-19
    Changes: Data collection, Database references
  • Version 1.2: 2023-11-22
    Changes: Data collection, Database references, Refinement description