8pqo: Difference between revisions
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==PITP in complex with the inhibitor VT01545== | |||
<StructureSection load='8pqo' size='340' side='right'caption='[[8pqo]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8pqo]] 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=8PQO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PQO 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BU4:(3R)-BUTANE-1,3-DIOL'>BU4</scene>, <scene name='pdbligand=F8O:(2~{R},4~{R})-2,4-dimethyloctanal'>F8O</scene>, <scene name='pdbligand=FDO:(2~{R})-4-methyl-2-(methylamino)pentanamide'>FDO</scene>, <scene name='pdbligand=FH6:(2~{R})-2-azanyl-3-[(2~{S},3~{R})-2-methyl-5-oxidanylidene-pyrrolidin-3-yl]sulfanyl-propanal'>FH6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=MV9:(2~{R})-3-METHYL-2-(METHYLAMINO)BUTANOIC+ACID'>MV9</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=UYA:(4R)-4-hydroxy-D-proline'>UYA</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=8pqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pqo OCA], [https://pdbe.org/8pqo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pqo RCSB], [https://www.ebi.ac.uk/pdbsum/8pqo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pqo ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PIPNA_HUMAN PIPNA_HUMAN] Catalyzes the transfer of PtdIns and phosphatidylcholine between membranes. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Phosphatidylinositol (PI) is the precursor lipid for the minor phosphoinositides (PPIns), which are critical for multiple functions in all eukaryotic cells. It is poorly understood how phosphatidylinositol, which is synthesized in the ER, reaches those membranes where PPIns are formed. Here, we used VT01454, a recently identified inhibitor of class I PI transfer proteins (PITPs), to unravel their roles in lipid metabolism, and solved the structure of inhibitor-bound PITPNA to gain insight into the mode of inhibition. We found that class I PITPs not only distribute PI for PPIns production in various organelles such as the plasma membrane (PM) and late endosomes/lysosomes, but that their inhibition also significantly reduced the levels of phosphatidylserine, di- and triacylglycerols, and other lipids, and caused prominent increases in phosphatidic acid. While VT01454 did not inhibit Golgi PI4P formation nor reduce resting PM PI(4,5)P(2) levels, the recovery of the PM pool of PI(4,5)P(2) after receptor-mediated hydrolysis required both class I and class II PITPs. Overall, these studies show that class I PITPs differentially regulate phosphoinositide pools and affect the overall cellular lipid landscape. | |||
Non-vesicular phosphatidylinositol transfer plays critical roles in defining organelle lipid composition.,Kim YJ, Pemberton JG, Eisenreichova A, Mandal A, Koukalova A, Rohilla P, Sohn M, Konradi AW, Tang TT, Boura E, Balla T EMBO J. 2024 Apr 16. doi: 10.1038/s44318-024-00096-3. PMID:38627600<ref>PMID:38627600</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8pqo" style="background-color:#fffaf0;"></div> | ||
[[Category: Boura | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Boura E]] | |||
[[Category: Eisenreichova A]] | |||
Latest revision as of 08:32, 9 May 2024
PITP in complex with the inhibitor VT01545
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