6bii

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

spinqualitylabelsall models 6bii, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bii is a 2 chain structure with sequence from Pyrococcus yayanosii CH1. This structure supersedes the now removed PDB entry 5aow. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: GOL, MLI, NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F8AEA4_PYRYC Publication Abstract from PubMed 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 A 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 A 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. New insights into the mechanism of substrates trafficking in Glyoxylate/Hydroxypyruvate reductases.,Lassalle L, Engilberge S, Madern D, Vauclare P, Franzetti B, Girard E Sci Rep. 2016 Feb 11;6:20629. doi: 10.1038/srep20629. PMID:26865263 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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