7wte
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7wte]] 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=7WTE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WTE FirstGlance]. <br> | <table><tr><td colspan='2'>[[7wte]] 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=7WTE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WTE FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></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=7wte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wte OCA], [https://pdbe.org/7wte PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wte RCSB], [https://www.ebi.ac.uk/pdbsum/7wte PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wte 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=7wte FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wte OCA], [https://pdbe.org/7wte PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wte RCSB], [https://www.ebi.ac.uk/pdbsum/7wte PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wte ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Pyruvate carboxylase (PC) catalyzes the two-step carboxylation of pyruvate to produce oxaloacetate, playing a key role in the maintenance of metabolic homeostasis in cells. Given its involvement in multiple diseases, PC has been regarded as a potential therapeutic target for obesity, diabetes, and cancer. Albeit acetyl-CoA has been recognized as the allosteric regulator of PC for over 60 years, the underlying mechanism of how acetyl-CoA induces PC activation remains enigmatic. Herein, by using time-resolved cryo-electron microscopy, we have captured the snapshots of PC transitional states during its catalytic cycle. These structures and the biochemical studies reveal that acetyl-CoA stabilizes PC in a catalytically competent conformation, which triggers a cascade of events, including ATP hydrolysis and the long-distance communication between the two reactive centers. These findings provide an integrated picture for PC catalysis and unveil the unique allosteric mechanism of acetyl-CoA in an essential biochemical reaction in all kingdoms of life. | Pyruvate carboxylase (PC) catalyzes the two-step carboxylation of pyruvate to produce oxaloacetate, playing a key role in the maintenance of metabolic homeostasis in cells. Given its involvement in multiple diseases, PC has been regarded as a potential therapeutic target for obesity, diabetes, and cancer. Albeit acetyl-CoA has been recognized as the allosteric regulator of PC for over 60 years, the underlying mechanism of how acetyl-CoA induces PC activation remains enigmatic. Herein, by using time-resolved cryo-electron microscopy, we have captured the snapshots of PC transitional states during its catalytic cycle. These structures and the biochemical studies reveal that acetyl-CoA stabilizes PC in a catalytically competent conformation, which triggers a cascade of events, including ATP hydrolysis and the long-distance communication between the two reactive centers. These findings provide an integrated picture for PC catalysis and unveil the unique allosteric mechanism of acetyl-CoA in an essential biochemical reaction in all kingdoms of life. | ||
| - | Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA.,Chai P, Lan P, Li S, Yao D, Chang C, Cao M, Shen Y, Ge S, Wu J, Lei M, Fan X Mol Cell. 2022 Nov 3;82(21):4116-4130.e6. doi: 10.1016/j.molcel.2022.09.033. Epub, 2022 Oct 24. PMID:36283412<ref>PMID:36283412</ref> | + | Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA.,Chai P, Lan P, Li S, Yao D, Chang C, Cao M, Shen Y, Ge S, Wu J, Lei M, Fan X Mol Cell. 2022 Nov 3;82(21):4116-4130.e6. doi: 10.1016/j.molcel.2022.09.033. Epub , 2022 Oct 24. PMID:36283412<ref>PMID:36283412</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7wte" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7wte" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Pyruvate carboxylase 3D structures|Pyruvate carboxylase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 2
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Categories: Homo sapiens | Large Structures | Chai P | Lan P | Lei M | Wu J
