5AOV

Ternary Crystal Structure of Pyrococcus furiosus Glyoxylate Hydroxypyruvate Reductase in presence of glyoxylate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.143 
  • R-Value Work: 0.131 
  • R-Value Observed: 0.132 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

New Insights Into the Mechanism of Substrates Trafficking in Glyoxylate/Hydroxypyruvate Reductases.

Lassalle, L.Engilberge, S.Madern, D.Vauclare, P.Franzetti, B.Girard, E.

(2016) Sci Rep 6: 20629

  • DOI: https://doi.org/10.1038/srep20629
  • Primary Citation of Related Structures:  
    5AOV, 6BII

  • PubMed Abstract: 

    Glyoxylate accumulation within cells is highly toxic. In humans, it is associated with hyperoxaluria type 2 (PH2) leading to renal failure. The glyoxylate content within cells is regulated by the NADPH/NADH dependent glyoxylate/hydroxypyruvate reductases (GRHPR). These are highly conserved enzymes with a dual activity as they are able to reduce glyoxylate to glycolate and to convert hydroxypyruvate into D-glycerate. Despite the determination of high-resolution X-ray structures, the substrate recognition mode of this class of enzymes remains unclear. We determined the structure at 2.0 Å resolution of a thermostable GRHPR from Archaea as a ternary complex in the presence of D-glycerate and NADPH. This shows a binding mode conserved between human and archeal enzymes. We also determined the first structure of GRHPR in presence of glyoxylate at 1.40 Å resolution. This revealed the pivotal role of Leu53 and Trp138 in substrate trafficking. These residues act as gatekeepers at the entrance of a tunnel connecting the active site to protein surface. Taken together, these results allowed us to propose a general model for GRHPR mode of action.


  • Organizational Affiliation

    Univ. Grenoble Alpes, IBS, F-38044 Grenoble, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GLYOXYLATE REDUCTASE336Pyrococcus furiosusMutation(s): 0 
EC: 1.1.1.26 (PDB Primary Data), 1.1.1.81 (PDB Primary Data), 1.1.1.79 (PDB Primary Data)
UniProt
Find proteins for Q8U3Y2 (Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1))
Explore Q8U3Y2 
Go to UniProtKB:  Q8U3Y2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8U3Y2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP

Download Ideal Coordinates CCD File 
B [auth A]NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
1PE
Query on 1PE

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
G [auth A]
H [auth A]
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
V [auth A],
Z [auth A]
PENTAETHYLENE GLYCOL
C10 H22 O6
JLFNLZLINWHATN-UHFFFAOYSA-N
GLV
Query on GLV

Download Ideal Coordinates CCD File 
C [auth A],
W [auth A]
GLYOXYLIC ACID
C2 H2 O3
HHLFWLYXYJOTON-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
Q [auth A],
R [auth A],
S [auth A],
T [auth A],
U [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
ACY
Query on ACY

Download Ideal Coordinates CCD File 
X [auth A],
Y [auth A]
ACETIC ACID
C2 H4 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.143 
  • R-Value Work: 0.131 
  • R-Value Observed: 0.132 
  • Space Group: I 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 114.579α = 90
b = 114.579β = 90
c = 118.123γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
SHELXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-03-02
    Type: Initial release
  • Version 2.0: 2019-10-23
    Changes: Atomic model, Data collection, Other
  • Version 2.1: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Structure summary