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7l9x
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7l9x is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of VPS4B in complex with an allele-specific covalent inhibitor== | |
| + | <StructureSection load='7l9x' size='340' side='right'caption='[[7l9x]], [[Resolution|resolution]] 2.81Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7l9x]] 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=7L9X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L9X 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]] 2.81Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XQV:N-{3-[(8-phenyl[1,2,4]triazolo[1,5-a]pyridin-2-yl)amino]phenyl}propanamide'>XQV</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=7l9x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l9x OCA], [https://pdbe.org/7l9x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l9x RCSB], [https://www.ebi.ac.uk/pdbsum/7l9x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l9x ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/VPS4B_HUMAN VPS4B_HUMAN] Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses).<ref>PMID:11563910</ref> <ref>PMID:14505570</ref> <ref>PMID:18687924</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The structural conservation across the AAA (ATPases associated with diverse cellular activities) protein family makes designing selective chemical inhibitors challenging. Here, we identify a triazolopyridine-based fragment that binds the AAA domain of human katanin, a microtubule-severing protein. We have developed a model for compound binding and designed ASPIR-1 (allele-specific, proximity-induced reactivity-based inhibitor-1), a cell-permeable compound that selectively inhibits katanin with an engineered cysteine mutation. Only in cells expressing mutant katanin does ASPIR-1 treatment increase the accumulation of CAMSAP2 at microtubule minus ends, confirming specific on-target cellular activity. Importantly, ASPIR-1 also selectively inhibits engineered cysteine mutants of human VPS4B and FIGL1-AAA proteins, involved in organelle dynamics and genome stability, respectively. Structural studies confirm our model for compound binding at the AAA ATPase site and the proximity-induced reactivity-based inhibition. Together, our findings suggest a chemical genetics approach to decipher AAA protein functions across essential cellular processes and to test hypotheses for developing therapeutics. | ||
| - | + | A chemical genetics approach to examine the functions of AAA proteins.,Cupido T, Jones NH, Grasso MJ, Pisa R, Kapoor TM Nat Struct Mol Biol. 2021 Mar 29. pii: 10.1038/s41594-021-00575-9. doi:, 10.1038/s41594-021-00575-9. PMID:33782614<ref>PMID:33782614</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7l9x" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Vacuolar protein sorting-associated protein 3D structures|Vacuolar protein sorting-associated protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cupido T]] | ||
| + | [[Category: Grasso M]] | ||
| + | [[Category: Kapoor TM]] | ||
Current revision
Structure of VPS4B in complex with an allele-specific covalent inhibitor
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