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4yw8

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Revision as of 07:28, 10 May 2023

Structure of rat cytosolic pepck in complex with 3-mercaptopicolinic acid

Structural highlights

4yw8 is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4yw8"

@@ Line 3: / Line 3: @@
 <StructureSection load='4yw8' size='340' side='right'caption='[[4yw8]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4yw8]] 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=4YW8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YW8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4yw8]] 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=4YW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YW8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1WD:3-SULFANYLPYRIDINE-2-CARBOXYLIC+ACID'>1WD</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MEE:METHANETHIOL'>MEE</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MOH:METHANOL'>MOH</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1WD:3-SULFANYLPYRIDINE-2-CARBOXYLIC+ACID'>1WD</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MEE:METHANETHIOL'>MEE</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MOH:METHANOL'>MOH</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yw8 OCA], [https://pdbe.org/4yw8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yw8 RCSB], [https://www.ebi.ac.uk/pdbsum/4yw8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yw8 ProSAT]</span></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=4yw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yw8 OCA], [http://pdbe.org/4yw8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yw8 RCSB], [http://www.ebi.ac.uk/pdbsum/4yw8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yw8 ProSAT]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Buffalo rat]]
 [[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]]
-[[Category: Transferase]]

4yw8

From Proteopedia

Revision as of 07:28, 10 May 2023

Structure of rat cytosolic pepck in complex with 3-mercaptopicolinic acid

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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