6b3v: Difference between revisions
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==PANK3 complex with compound PZ-2891== | ==PANK3 complex with compound PZ-2891== | ||
<StructureSection load='6b3v' size='340' side='right' caption='[[6b3v]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='6b3v' size='340' side='right'caption='[[6b3v]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6b3v]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B3V OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6b3v]] 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=6B3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B3V FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7DQ:6-(4-{[4-(propan-2-yl)phenyl]acetyl}piperazin-1-yl)pyridazine-3-carbonitrile'>7DQ</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.601Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7DQ:6-(4-{[4-(propan-2-yl)phenyl]acetyl}piperazin-1-yl)pyridazine-3-carbonitrile'>7DQ</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6b3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b3v OCA], [https://pdbe.org/6b3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b3v RCSB], [https://www.ebi.ac.uk/pdbsum/6b3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b3v ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/PANK3_HUMAN PANK3_HUMAN] Plays a role in the physiological regulation of the intracellular CoA concentration (By similarity). | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pantothenate kinase (PANK) is a metabolic enzyme that regulates cellular coenzyme A (CoA) levels. There are three human PANK genes, and inactivating mutations in PANK2 lead to pantothenate kinase associated neurodegeneration (PKAN). Here we performed a library screen followed by chemical optimization to produce PZ-2891, an allosteric PANK activator that crosses the blood brain barrier. PZ-2891 occupies the pantothenate pocket and engages the dimer interface to form a PANK*ATP*Mg(2+)*PZ-2891 complex. The binding of PZ-2891 to one protomer locks the opposite protomer in a catalytically active conformation that is refractory to acetyl-CoA inhibition. Oral administration of PZ-2891 increases CoA levels in mouse liver and brain. A knockout mouse model of brain CoA deficiency exhibited weight loss, severe locomotor impairment and early death. Knockout mice on PZ-2891 therapy gain weight, and have improved locomotor activity and life span establishing pantazines as novel therapeutics for the treatment of PKAN. | |||
A therapeutic approach to pantothenate kinase associated neurodegeneration.,Sharma LK, Subramanian C, Yun MK, Frank MW, White SW, Rock CO, Lee RE, Jackowski S Nat Commun. 2018 Oct 23;9(1):4399. doi: 10.1038/s41467-018-06703-2. PMID:30352999<ref>PMID:30352999</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6b3v" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Pantothenate kinase 3D structures|Pantothenate kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: White SW]] | ||
[[Category: | [[Category: Yun M]] | ||
Latest revision as of 14:32, 4 October 2023
PANK3 complex with compound PZ-2891
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