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| | <StructureSection load='2wwr' size='340' side='right'caption='[[2wwr]], [[Resolution|resolution]] 2.82Å' scene=''> | | <StructureSection load='2wwr' size='340' side='right'caption='[[2wwr]], [[Resolution|resolution]] 2.82Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wwr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WWR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WWR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wwr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WWR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WWR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.82Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2h1s|2h1s]], [[2gcg|2gcg]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glyoxylate_reductase_(NADP(+)) Glyoxylate reductase (NADP(+))], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.79 1.1.1.79] </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=2wwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wwr OCA], [https://pdbe.org/2wwr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wwr RCSB], [https://www.ebi.ac.uk/pdbsum/2wwr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wwr ProSAT]</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=2wwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wwr OCA], [https://pdbe.org/2wwr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wwr RCSB], [https://www.ebi.ac.uk/pdbsum/2wwr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wwr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/GRHPR_HUMAN GRHPR_HUMAN]] Defects in GRHPR are the cause of hyperoxaluria primary type 2 (HP2) [MIM:[https://omim.org/entry/260000 260000]]; also known as primary hyperoxaluria type II (PH2). HP2 is a disorder where the main clinical manifestation is calcium oxalate nephrolithiasis though chronic as well as terminal renal insufficiency has been described. It is characterized by an elevated urinary excretion of oxalate and L-glycerate.<ref>PMID:10484776</ref>
| + | [https://www.uniprot.org/uniprot/GRHPR_HUMAN GRHPR_HUMAN] Defects in GRHPR are the cause of hyperoxaluria primary type 2 (HP2) [MIM:[https://omim.org/entry/260000 260000]; also known as primary hyperoxaluria type II (PH2). HP2 is a disorder where the main clinical manifestation is calcium oxalate nephrolithiasis though chronic as well as terminal renal insufficiency has been described. It is characterized by an elevated urinary excretion of oxalate and L-glycerate.<ref>PMID:10484776</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GRHPR_HUMAN GRHPR_HUMAN]] Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Reduces hydroxypyruvate to D-glycerate, glyoxylate to glycolate oxidizes D-glycerate to hydroxypyruvate.
| + | [https://www.uniprot.org/uniprot/GRHPR_HUMAN GRHPR_HUMAN] Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Reduces hydroxypyruvate to D-glycerate, glyoxylate to glycolate oxidizes D-glycerate to hydroxypyruvate. |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Booth, M P.S]] | + | [[Category: Booth MPS]] |
| - | [[Category: Brady, R L]] | + | [[Category: Brady RL]] |
| - | [[Category: Conners, R]] | + | [[Category: Conners R]] |
| - | [[Category: Rumsby, G]] | + | [[Category: Rumsby G]] |
| - | [[Category: Molecular conformation]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Disease
GRHPR_HUMAN Defects in GRHPR are the cause of hyperoxaluria primary type 2 (HP2) [MIM:260000; also known as primary hyperoxaluria type II (PH2). HP2 is a disorder where the main clinical manifestation is calcium oxalate nephrolithiasis though chronic as well as terminal renal insufficiency has been described. It is characterized by an elevated urinary excretion of oxalate and L-glycerate.[1]
Function
GRHPR_HUMAN Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Reduces hydroxypyruvate to D-glycerate, glyoxylate to glycolate oxidizes D-glycerate to hydroxypyruvate.
Publication Abstract from PubMed
Human glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is a D-2-hydroxy-acid dehydrogenase that plays a critical role in the removal of the metabolic by-product glyoxylate from within the liver. Deficiency of this enzyme is the underlying cause of primary hyperoxaluria type 2 (PH2) and leads to increased urinary oxalate levels, formation of kidney stones and renal failure. Here we describe the crystal structure of human GRHPR at 2.2 A resolution. There are four copies of GRHPR in the crystallographic asymmetric unit: in each homodimer, one subunit forms a ternary (enzyme+NADPH+reduced substrate) complex, and the other a binary (enzyme+NADPH) form. The spatial arrangement of the two enzyme domains is the same in binary and ternary forms. This first crystal structure of a true ternary complex of an enzyme from this family demonstrates the relationship of substrate and catalytic residues within the active site, confirming earlier proposals of the mode of substrate binding, stereospecificity and likely catalytic mechanism for these enzymes. GRHPR has an unusual substrate specificity, preferring glyoxylate and hydroxypyruvate, but not pyruvate. A tryptophan residue (Trp141) from the neighbouring subunit of the dimer is projected into the active site region and appears to contribute to the selectivity for hydroxypyruvate. This first crystal structure of a human GRHPR enzyme also explains the deleterious effects of naturally occurring missense mutations of this enzyme that lead to PH2.
Structural basis of substrate specificity in human glyoxylate reductase/hydroxypyruvate reductase.,Booth MP, Conners R, Rumsby G, Brady RL J Mol Biol. 2006 Jun 30;360(1):178-89. Epub 2006 May 22. PMID:16756993[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cramer SD, Ferree PM, Lin K, Milliner DS, Holmes RP. The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II. Hum Mol Genet. 1999 Oct;8(11):2063-9. PMID:10484776
- ↑ Booth MP, Conners R, Rumsby G, Brady RL. Structural basis of substrate specificity in human glyoxylate reductase/hydroxypyruvate reductase. J Mol Biol. 2006 Jun 30;360(1):178-89. Epub 2006 May 22. PMID:16756993 doi:10.1016/j.jmb.2006.05.018
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