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| | <StructureSection load='4ywd' size='340' side='right'caption='[[4ywd]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='4ywd' size='340' side='right'caption='[[4ywd]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ywd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YWD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ywd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YWD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YWD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NTM:QUINOLINIC+ACID'>NTM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NTM:QUINOLINIC+ACID'>NTM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wy8|4wy8]], [[4wy9|4wy9]], [[4wyb|4wyb]]</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=4ywd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ywd OCA], [https://pdbe.org/4ywd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ywd RCSB], [https://www.ebi.ac.uk/pdbsum/4ywd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ywd ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pck1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoenolpyruvate_carboxykinase_(GTP) Phosphoenolpyruvate carboxykinase (GTP)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.32 4.1.1.32] </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=4ywd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ywd OCA], [http://pdbe.org/4ywd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ywd RCSB], [http://www.ebi.ac.uk/pdbsum/4ywd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ywd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PCKGC_RAT PCKGC_RAT]] Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. | + | [https://www.uniprot.org/uniprot/PCKGC_RAT PCKGC_RAT] Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. |
| | <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: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Balan, M D]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Holyoak, T]] | + | [[Category: Balan MD]] |
| - | [[Category: Johnson, T A]] | + | [[Category: Holyoak T]] |
| - | [[Category: Lotosky, W R]] | + | [[Category: Johnson TA]] |
| - | [[Category: Mcleod, M J]] | + | [[Category: Lotosky WR]] |
| - | [[Category: Gluconeogenesis]] | + | [[Category: Mcleod MJ]] |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
Function
PCKGC_RAT Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.
Publication Abstract from PubMed
For almost 40 years, it has been known that tryptophan metabolites and picolinic acid analogues act as inhibitors of gluconeogenesis. Early studies observed that 3-mercaptopicolinic acid (MPA) was a potent hypoglycemic agent via inhibition of glucose synthesis through the specific inhibition of phosphoenolpyruvate carboxykinase (PEPCK) in the gluconeogenesis pathway. Despite prior kinetic investigation, the mechanism of the inhibition by MPA is unclear. To clarify the mechanism of inhibition exerted by MPA on PEPCK, we have undertaken structural and kinetic studies. The kinetic data in concert with crystallographic structures of PEPCK in complex with MPA and the substrates for the reaction illustrate that PEPCK is inhibited by the binding of MPA at two discrete binding sites: one acting in a competitive fashion with PEP/OAA ( approximately 10 muM) and the other acting at a previously unidentified allosteric site (Ki approximately 150 muM). The structural studies suggest that binding of MPA to the allosteric pocket stabilizes an altered conformation of the nucleotide-binding site that in turn reduces the affinity of the enzyme for the nucleotide.
Inhibition and Allosteric Regulation of Monomeric Phosphoenolpyruvate Carboxykinase by 3-Mercaptopicolinic Acid.,Balan MD, Mcleod MJ, Lotosky WR, Ghaly M, Holyoak T Biochemistry. 2015 Sep 29;54(38):5878-87. doi: 10.1021/acs.biochem.5b00822. Epub , 2015 Sep 11. PMID:26322521[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Balan MD, Mcleod MJ, Lotosky WR, Ghaly M, Holyoak T. Inhibition and Allosteric Regulation of Monomeric Phosphoenolpyruvate Carboxykinase by 3-Mercaptopicolinic Acid. Biochemistry. 2015 Sep 29;54(38):5878-87. doi: 10.1021/acs.biochem.5b00822. Epub , 2015 Sep 11. PMID:26322521 doi:http://dx.doi.org/10.1021/acs.biochem.5b00822
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