7wte
From Proteopedia
(Difference between revisions)
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- | '''Unreleased structure''' | ||
- | + | ==Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 2== | |
+ | <StructureSection load='7wte' size='340' side='right'caption='[[7wte]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
+ | == 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> | ||
+ | </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> | ||
+ | </table> | ||
+ | == Disease == | ||
+ | [https://www.uniprot.org/uniprot/PYC_HUMAN PYC_HUMAN] Defects in PC are the cause of pyruvate carboxylase deficiency (PC deficiency) [MIM:[https://omim.org/entry/266150 266150]. PC deficiency leads to lactic acidosis, mental retardation and death. It occurs in three forms: mild or type A, severe neonatal or type B, and a very mild lacticacidemia. | ||
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/PYC_HUMAN PYC_HUMAN] Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. Catalyzes in a tissue specific manner, the initial reactions of glucose (liver, kidney) and lipid (adipose tissue, liver, brain) synthesis from pyruvate. | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | 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> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | [[Category: | + | </div> |
- | [[Category: | + | <div class="pdbe-citations 7wte" style="background-color:#fffaf0;"></div> |
- | [[Category: | + | == References == |
- | [[Category: | + | <references/> |
- | [[Category: Lei | + | __TOC__ |
+ | </StructureSection> | ||
+ | [[Category: Homo sapiens]] | ||
+ | [[Category: Large Structures]] | ||
+ | [[Category: Chai P]] | ||
+ | [[Category: Lan P]] | ||
+ | [[Category: Lei M]] | ||
+ | [[Category: Wu J]] |
Revision as of 07:26, 9 November 2022
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