4o3f: Difference between revisions
New page: '''Unreleased structure''' The entry 4o3f is ON HOLD Authors: Li X.L., Finci I.L., Wang J.H. Description: Crystal Structure of mouse PGK1 3PG and terazosin(TZN) ternary complex |
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==Crystal Structure of mouse PGK1 3PG and terazosin(TZN) ternary complex== | |||
<StructureSection load='4o3f' size='340' side='right'caption='[[4o3f]], [[Resolution|resolution]] 2.11Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4o3f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O3F FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.106Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PG:3-PHOSPHOGLYCERIC+ACID'>3PG</scene>, <scene name='pdbligand=TZN:[4-(4-AMINO-6,7-DIMETHOXYQUINAZOLIN-2-YL)PIPERAZIN-1-YL][(2R)-TETRAHYDROFURAN-2-YL]METHANONE'>TZN</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=4o3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o3f OCA], [https://pdbe.org/4o3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o3f RCSB], [https://www.ebi.ac.uk/pdbsum/4o3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o3f ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PGK1_MOUSE PGK1_MOUSE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Drugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We discovered that terazosin (TZ), a widely marketed alpha1-adrenergic receptor antagonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we discovered that TZ binds a new target, phosphoglycerate kinase 1 (Pgk1), and activates its enzymatic activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multistress resistance. Our studies demonstrate that TZ has a new protein target, Pgk1, and reveal its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatments for diseases including stroke and sepsis. | |||
Terazosin activates Pgk1 and Hsp90 to promote stress resistance.,Chen X, Zhao C, Li X, Wang T, Li Y, Cao C, Ding Y, Dong M, Finci L, Wang JH, Li X, Liu L Nat Chem Biol. 2014 Nov 10. doi: 10.1038/nchembio.1657. PMID:25383758<ref>PMID:25383758</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4o3f" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Phosphoglycerate kinase 3D structures|Phosphoglycerate kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Finci IL]] | |||
[[Category: Li XL]] | |||
[[Category: Wang JH]] | |||
Latest revision as of 20:06, 20 September 2023
Crystal Structure of mouse PGK1 3PG and terazosin(TZN) ternary complexCrystal Structure of mouse PGK1 3PG and terazosin(TZN) ternary complex
Structural highlights
FunctionPublication Abstract from PubMedDrugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We discovered that terazosin (TZ), a widely marketed alpha1-adrenergic receptor antagonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we discovered that TZ binds a new target, phosphoglycerate kinase 1 (Pgk1), and activates its enzymatic activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multistress resistance. Our studies demonstrate that TZ has a new protein target, Pgk1, and reveal its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatments for diseases including stroke and sepsis. Terazosin activates Pgk1 and Hsp90 to promote stress resistance.,Chen X, Zhao C, Li X, Wang T, Li Y, Cao C, Ding Y, Dong M, Finci L, Wang JH, Li X, Liu L Nat Chem Biol. 2014 Nov 10. doi: 10.1038/nchembio.1657. PMID:25383758[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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