5AOV

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

PDB DOI: https://doi.org/10.2210/pdb5AOV/pdb

Classification: OXIDOREDUCTASE
Organism(s): Pyrococcus furiosus
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2015-09-12 Released: 2016-03-02
Deposition Author(s): Lassalle, L., Girard, E.

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

wwPDB Validation 3D Report Full Report

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

PubMed: 26865263 Search on PubMedSearch on PubMed Central
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.

Macromolecule Content

Total Structure Weight: 43.29 kDa
Atom Count: 3,521
Modelled Residue Count: 334
Deposited Residue Count: 336
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
GLYOXYLATE REDUCTASE	A	336	Pyrococcus furiosus	Mutation(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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q8U3Y2
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAP Query on NAP Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE C₂₁ H₂₈ N₇ O₁₇ P₃ XJLXINKUBYWONI-NNYOXOHSSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
1PE Query on 1PE Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain N [auth A] SDF format, chain O [auth A] SDF format, chain P [auth A] SDF format, chain Z [auth A] SDF format, chain E [auth A] SDF format, chain I [auth A] SDF format, chain M [auth A] SDF format, chain V [auth A] MOL2 format, chain D [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain N [auth A] MOL2 format, chain O [auth A] MOL2 format, chain P [auth A] MOL2 format, chain Z [auth A] MOL2 format, chain E [auth A] MOL2 format, chain I [auth A] MOL2 format, chain M [auth A] MOL2 format, chain V [auth A] mmCIF format, chain D [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain L [auth A] mmCIF format, chain N [auth A] mmCIF format, chain O [auth A] mmCIF format, chain P [auth A] mmCIF format, chain Z [auth A] mmCIF format, chain E [auth A] mmCIF format, chain I [auth A] mmCIF format, chain M [auth A] mmCIF format, chain V [auth A]	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		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain V [auth A] Focus chain Z [auth A] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain V [auth A] Focus chain Z [auth A]
GLV Query on GLV Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain W [auth A] MOL2 format, chain C [auth A] MOL2 format, chain W [auth A] mmCIF format, chain C [auth A] mmCIF format, chain W [auth A]	C [auth A], W [auth A]	GLYOXYLIC ACID C₂ H₂ O₃ HHLFWLYXYJOTON-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain W [auth A] Interactions & Density Focus chain C [auth A] Focus chain W [auth A]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain R [auth A] SDF format, chain T [auth A] SDF format, chain U [auth A] SDF format, chain Q [auth A] SDF format, chain S [auth A] MOL2 format, chain R [auth A] MOL2 format, chain T [auth A] MOL2 format, chain U [auth A] MOL2 format, chain Q [auth A] MOL2 format, chain S [auth A] mmCIF format, chain R [auth A] mmCIF format, chain T [auth A] mmCIF format, chain U [auth A] mmCIF format, chain Q [auth A] mmCIF format, chain S [auth A]	Q [auth A], R [auth A], S [auth A], T [auth A], U [auth A]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A] Interactions & Density Focus chain Q [auth A] Focus chain R [auth A] Focus chain S [auth A] Focus chain T [auth A] Focus chain U [auth A]
ACY Query on ACY Download Ideal Coordinates CCD File SDF format, chain X [auth A] SDF format, chain Y [auth A] MOL2 format, chain X [auth A] MOL2 format, chain Y [auth A] mmCIF format, chain X [auth A] mmCIF format, chain Y [auth A]	X [auth A], Y [auth A]	ACETIC ACID C₂ H₄ O₂ QTBSBXVTEAMEQO-UHFFFAOYSA-N		Interactions Focus chain X [auth A] Focus chain Y [auth A] Interactions & Density Focus chain X [auth A] Focus chain Y [auth A]

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 = 114.579	α = 90
b = 114.579	β = 90
c = 118.123	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
XDS	data reduction
SCALA	data scaling
SHELX	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2016-03-02

Deposition Author(s):

Lassalle, L.

Girard, E.

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