7fry - Revision history

OCA at 10:31, 22 May 2024

2024-05-22T10:31:52Z

←Older revision		Revision as of 10:31, 22 May 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7fry]] is a 8 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=7FRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FRY FirstGlance]. <br>		<table><tr><td colspan='2'>[[7fry]] is a 8 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=7FRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FRY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=Y0T:N-{2-[4-(3,4-dihydroxybenzene-1-sulfonyl)phenyl]ethyl}-3,4-dihydroxybenzene-1-sulfonamide'>Y0T</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.958Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=Y0T:N-{2-[4-(3,4-dihydroxybenzene-1-sulfonyl)phenyl]ethyl}-3,4-dihydroxybenzene-1-sulfonamide'>Y0T</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=7fry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fry OCA], [https://pdbe.org/7fry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fry RCSB], [https://www.ebi.ac.uk/pdbsum/7fry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fry 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=7fry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fry OCA], [https://pdbe.org/7fry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fry RCSB], [https://www.ebi.ac.uk/pdbsum/7fry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fry ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7fry" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7fry" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Pyruvate kinase 3D structures\|Pyruvate kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 20:24, 12 April 2023

2023-04-12T20:24:36Z

←Older revision		Revision as of 20:24, 12 April 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 7fry is ~~ON HOLD~~	+	==Structure of liver pyruvate kinase in complex with allosteric modulator 6==
		+	<StructureSection load='7fry' size='340' side='right'caption='[[7fry]], [[Resolution\|resolution]] 1.96Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7fry]] is a 8 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=7FRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FRY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=Y0T:N-{2-[4-(3,4-dihydroxybenzene-1-sulfonyl)phenyl]ethyl}-3,4-dihydroxybenzene-1-sulfonamide'>Y0T</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=7fry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fry OCA], [https://pdbe.org/7fry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fry RCSB], [https://www.ebi.ac.uk/pdbsum/7fry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fry ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/KPYR_HUMAN KPYR_HUMAN] Defects in PKLR are the cause of pyruvate kinase hyperactivity (PKHYP) [MIM:[https://omim.org/entry/102900 102900]; also known as high red cell ATP syndrome. This autosomal dominant phenotype is characterized by increase of red blood cell ATP.<ref>PMID:9090535</ref> Defects in PKLR are the cause of pyruvate kinase deficiency of red cells (PKRD) [MIM:[https://omim.org/entry/266200 266200]. A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/KPYR_HUMAN KPYR_HUMAN] Plays a key role in glycolysis (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The liver isoform of pyruvate kinase (PKL) has gained interest due to its potential capacity to regulate fatty acid synthesis involved in the progression of non-alcoholic fatty liver disease (NAFLD). Here we describe a novel series of PKL modulators that can either activate or inhibit the enzyme allosterically, from a cryptic site at the interface of two protomers in the tetrameric enzyme. Starting from urolithin D, we designed and synthesised 42 new compounds. The effect of these compounds on PKL enzymatic activity was assessed after incubation with cell lysates obtained from a liver cell line. Pronounced activation of PKL activity, up to 3.8-fold, was observed for several compounds at 10 muM, while other compounds were prominent PKL inhibitors reducing its activity to 81% at best. A structure-activity relationship identified linear-shaped sulfone-sulfonamides as activators and non-linear compounds as inhibitors. Crystal structures revealed the conformations of these modulators, which were used as a reference for designing new modulators.

-	~~Authors: Lulla~~, A., Nilsson, O., ~~Brear~~, P., ~~Nain-Perez~~, A., ~~Grotli~~, M., ~~Hyvonen, M~~.	+	Tuning liver pyruvate kinase activity up or down with a new class of allosteric modulators.,Nain-Perez A, Nilsson O, Lulla A, Haversen L, Brear P, Liljenberg S, Hyvonen M, Boren J, Grotli M Eur J Med Chem. 2023 Mar 15;250:115177. doi: 10.1016/j.ejmech.2023.115177. Epub , 2023 Feb 1. PMID:36753880<ref>PMID:36753880</ref>

-	~~Description: Structure~~ of ~~liver pyruvate kinase in complex with allosteric modulator 6~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Brear, P]]	+	<div class="pdbe-citations 7fry" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Hyvonen,~~ M]]	+	== References ==
-	[[Category: ~~Nilsson, O~~]]	+	<references/>
-	[[Category: Lulla, A]]	+	__TOC__
-	[[Category: ~~Grotli, M~~]]	+	</StructureSection>
-	[[Category: ~~Nain-Perez, A~~]]	+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Brear P]]
		+	[[Category: Grotli M]]
		+	[[Category: Hyvonen M]]
		+	[[Category: Lulla A]]
		+	[[Category: Nain-Perez A]]
		+	[[Category: Nilsson O]]

OCA: Protected "7fry" [edit=sysop:move=sysop]

2022-12-28T05:17:07Z

Protected "7fry" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:17, 28 December 2022

OCA: New page: '''Unreleased structure''' The entry 7fry is ON HOLD Authors: Lulla, A., Nilsson, O., Brear, P., Nain-Perez, A., Grotli, M., Hyvonen, M. Description: Structure of liver pyruvate kinase...

2022-12-28T05:17:04Z

New page: '''Unreleased structure''' The entry 7fry is ON HOLD Authors: Lulla, A., Nilsson, O., Brear, P., Nain-Perez, A., Grotli, M., Hyvonen, M. Description: Structure of liver pyruvate kinase...

New page

'''Unreleased structure'''

The entry 7fry is ON HOLD

Authors: Lulla, A., Nilsson, O., Brear, P., Nain-Perez, A., Grotli, M., Hyvonen, M.

Description: Structure of liver pyruvate kinase in complex with allosteric modulator 6
[[Category: Unreleased Structures]]
[[Category: Brear, P]]
[[Category: Hyvonen, M]]
[[Category: Nilsson, O]]
[[Category: Lulla, A]]
[[Category: Grotli, M]]
[[Category: Nain-Perez, A]]