5AOV
Ternary Crystal Structure of Pyrococcus furiosus Glyoxylate Hydroxypyruvate Reductase in presence of glyoxylate
Summary for 5AOV
| Entry DOI | 10.2210/pdb5aov/pdb |
| Related | 5AOW |
| Descriptor | GLYOXYLATE REDUCTASE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, GLYOXYLIC ACID, ... (7 entities in total) |
| Functional Keywords | oxidoreductase, glyoxylate hydroxypyruvate reductase, glyoxylate, archaea |
| Biological source | PYROCOCCUS FURIOSUS |
| Total number of polymer chains | 1 |
| Total formula weight | 43292.39 |
| Authors | Lassalle, L.,Girard, E. (deposition date: 2015-09-12, release date: 2016-03-02, Last modification date: 2024-05-08) |
| Primary citation | Lassalle, L.,Engilberge, S.,Madern, D.,Vauclare, P.,Franzetti, B.,Girard, E. New Insights Into the Mechanism of Substrates Trafficking in Glyoxylate/Hydroxypyruvate Reductases. Sci.Rep., 6:20629-, 2016 Cited by 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. PubMed: 26865263DOI: 10.1038/SREP20629 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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