6bii

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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)==
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<StructureSection load='6bii' size='340' side='right' caption='[[6bii]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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<StructureSection load='6bii' size='340' side='right'caption='[[6bii]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<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>
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<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>
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</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>
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</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&#8491;</td></tr>
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<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>
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<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>
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<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>
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<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>
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<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>
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</table>
</table>
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== Function ==
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[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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The d-2-hydroxyacid dehydrogenase (2HADH) family illustrates a complex evolutionary history with multiple lateral gene transfers and gene duplications and losses. As a result, the exact functional annotation of individual members can be extrapolated to a very limited extent. Here, we revise the previous simplified view on the classification of the 2HADH family; specifically, we show that the previously delineated glyoxylate/hydroxypyruvate reductase (GHPR) subfamily consists of two evolutionary separated GHRA and GHRB subfamilies. We compare two representatives of these subfamilies from Sinorhizobium meliloti (SmGhrA and SmGhrB), employing a combination of biochemical, structural, and bioinformatics approaches. Our kinetic results show that both enzymes reduce several 2-ketocarboxylic acids with overlapping, but not equivalent, substrate preferences. SmGhrA and SmGhrB show highest activity with glyoxylate and hydroxypyruvate, respectively; in addition, only SmGhrB reduces 2-keto-d-gluconate, and only SmGhrA reduces pyruvate (with low efficiency). We present nine crystal structures of both enzymes in apo forms and in complexes with cofactors and substrates/substrate analogues. In particular, we determined a crystal structure of SmGhrB with 2-keto-d-gluconate, which is the biggest substrate cocrystallized with a 2HADH member. The structures reveal significant differences between SmGhrA and SmGhrB, both in the overall structure and within the substrate-binding pocket, offering insight into the molecular basis for the observed substrate preferences and subfamily differences. In addition, we provide an overview of all GHRA and GHRB structures complexed with a ligand in the active site.
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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.
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Structural, Biochemical, and Evolutionary Characterizations of Glyoxylate/Hydroxypyruvate Reductases Show Their Division into Two Distinct Subfamilies.,Kutner J, Shabalin IG, Matelska D, Handing KB, Gasiorowska O, Sroka P, Gorna MW, Ginalski K, Wozniak K, Minor W Biochemistry. 2018 Jan 26. doi: 10.1021/acs.biochem.7b01137. PMID:29309127<ref>PMID:29309127</ref>
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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<ref>PMID:26865263</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Glyoxylate reductase]]
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[[Category: Large Structures]]
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[[Category: Pyryc]]
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[[Category: Pyrococcus yayanosii CH1]]
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[[Category: Girard, E]]
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[[Category: Girard E]]
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[[Category: Lassalle, L]]
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[[Category: Lassalle L]]
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[[Category: Minor, W]]
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[[Category: Minor W]]
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[[Category: Shabalin, I G]]
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[[Category: Shabalin IG]]
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[[Category: Ghrb]]
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[[Category: Hydroxypyruvate]]
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[[Category: Oxidoreductase]]
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[[Category: Reductase]]
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Current revision

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

PDB ID 6bii

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