6BII

Crystal Structure of Pyrococcus yayanosii Glyoxylate Hydroxypyruvate Reductase in complex with NADP and malonate (re-refinement of 5AOW)

Replaces:  5AOW

Summary for 6BII

• Entry DOI: 10.2210/pdb6bii/pdb
• Descriptor: Glyoxylate reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, MALONATE ION, ... (5 entities in total)
• Functional Keywords: hydroxypyruvate, reductase, ghrb, oxidoreductase
• Biological source: Pyrococcus yayanosii (strain CH1 / JCM 16557)
• Cellular location: Cytoplasm : F8AEA4
• Total number of polymer chains: 2
• Total formula weight: 77286.38

Authors

Lassalle, L.,Shabalin, I.G.,Girard, E.,Minor, W. (deposition date: 2017-11-02, release date: 2018-01-17, Last modification date: 2023-10-04)

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, 6:20629-20629, 2016

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: 26865263
DOI: 10.1038/srep20629

Experimental method

X-RAY DIFFRACTION (2 Å)