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| | ==Crystal Structure of Pyrococcus yayanosii Glyoxylate Hydroxypyruvate Reductase in complex with NADP and malonate (re-refinement of 5AOW)== | | ==Crystal Structure of Pyrococcus yayanosii Glyoxylate Hydroxypyruvate Reductase in complex with NADP and malonate (re-refinement of 5AOW)== |
| - | <StructureSection load='6bii' size='340' side='right' caption='[[6bii]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='6bii' size='340' side='right'caption='[[6bii]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bii]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Pyryc Pyryc]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5aow 5aow]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BII OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BII FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bii]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_yayanosii_CH1 Pyrococcus yayanosii CH1]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5aow 5aow]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BII OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BII FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gyaR, PYCH_09300 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=529709 PYRYC])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glyoxylate_reductase Glyoxylate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.26 1.1.1.26] </span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bii OCA], [https://pdbe.org/6bii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bii RCSB], [https://www.ebi.ac.uk/pdbsum/6bii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bii ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bii OCA], [http://pdbe.org/6bii PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bii RCSB], [http://www.ebi.ac.uk/pdbsum/6bii PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bii ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/F8AEA4_PYRYC F8AEA4_PYRYC] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glyoxylate reductase]] | + | [[Category: Large Structures]] |
| - | [[Category: Pyryc]] | + | [[Category: Pyrococcus yayanosii CH1]] |
| - | [[Category: Girard, E]] | + | [[Category: Girard E]] |
| - | [[Category: Lassalle, L]] | + | [[Category: Lassalle L]] |
| - | [[Category: Minor, W]] | + | [[Category: Minor W]] |
| - | [[Category: Shabalin, I G]] | + | [[Category: Shabalin IG]] |
| - | [[Category: Ghrb]]
| + | |
| - | [[Category: Hydroxypyruvate]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Reductase]]
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| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. 2016 Feb 11;6:20629. doi: 10.1038/srep20629. PMID:26865263 doi:http://dx.doi.org/10.1038/srep20629
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