9p0j: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
Tag: Manual revert
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
Line 1: Line 1:
'''Unreleased structure'''


The entry 9p0j is ON HOLD
==Human liver phosphofructokinase-1 bound to XJ-4-85==
<StructureSection load='9p0j' size='340' side='right'caption='[[9p0j]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9p0j]] is a 1 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=9P0J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9P0J FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1C4X:2H-1,3-benzodioxole-5-sulfonamide'>A1C4X</scene>, <scene name='pdbligand=A1CFQ:4-[bis[3,4-bis(fluoranyl)phenyl]methylidene]piperidine'>A1CFQ</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=F6P:FRUCTOSE-6-PHOSPHATE'>F6P</scene>, <scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</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=9p0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9p0j OCA], [https://pdbe.org/9p0j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9p0j RCSB], [https://www.ebi.ac.uk/pdbsum/9p0j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9p0j ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PFKAL_HUMAN PFKAL_HUMAN] Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis (PubMed:22923583). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by controlling cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen species. Upon macrophage activation, drives the metabolic switch toward glycolysis, thus preventing glucose turnover that produces NADPH via pentose phosphate pathway (By similarity).[UniProtKB:P12382][HAMAP-Rule:MF_03184]<ref>PMID:22923583</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glycolysis fuels vital cellular functions, and its dysregulation has been implicated in cancer, neurodegeneration, antibiotic resistance and diabetes. The glycolytic dependency of cancer, known as the Warburg effect, represents a key vulnerability for development of targeted anticancer agents; however, the development of such agents remains challenging owing to metabolic heterogeneity and resistance. Here we developed a covalent phosphofructokinase-1 liver type (PFKL) activator that couples glycolytic activation with delivery of a cytotoxic carnitine palmitoyltransferase 2 (CPT2)-targeting payload to cancer cells in vitro and in vivo. The electrophile-drug conjugate site-specifically and proteome-wide selectively modifies K677 in the allosteric effector site to stabilize the R-state tetramer of PFKL, while concomitantly releasing a CPT2-selective inhibitor to destabilize cell metabolism. The delivery mechanism of electrophile-drug conjugates is analogous to that of antibody-drug conjugates, but differentiated by their selective covalent targeting of intracellular proteins.


Authors:  
A covalent PFKL activator suppresses tumor growth.,Jiang X, Lynch EM, Lyu C, Wilson CN, Salay LE, Hess HT, Lyons SN, Lu MJ, Luo S, Kim G, Chan HR, Wolfe WJ, Zacharias LG, Mathews TP, Lin YC, Webb BA, Kollman JM, Cambronne XA, Hsu KL Nat Chem Biol. 2026 Aug 5. doi: 10.1038/s41589-026-02289-9. PMID:42557312<ref>PMID:42557312</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9p0j" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hsu K-L]]
[[Category: Jiang X]]
[[Category: Kollman JM]]
[[Category: Lynch EM]]
Retrieved from "https://proteopedia.org/9p0j"