6wys
From Proteopedia
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==Lon protease proteolytic domain== | ==Lon protease proteolytic domain== | ||
| - | <StructureSection load='6wys' size='340' side='right'caption='[[6wys]]' scene=''> | + | <StructureSection load='6wys' size='340' side='right'caption='[[6wys]], [[Resolution|resolution]] 2.23Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wys]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WYS FirstGlance]. <br> |
| - | </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=6wys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wys OCA], [https://pdbe.org/6wys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wys RCSB], [https://www.ebi.ac.uk/pdbsum/6wys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wys ProSAT]</span></td></tr> | + | </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></td></tr> |
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Endopeptidase_La Endopeptidase La], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.53 3.4.21.53] </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=6wys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wys OCA], [https://pdbe.org/6wys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wys RCSB], [https://www.ebi.ac.uk/pdbsum/6wys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wys ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/LONM_HUMAN LONM_HUMAN]] ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner. May regulate mitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters. Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein.[HAMAP-Rule:MF_03120]<ref>PMID:12198491</ref> <ref>PMID:15870080</ref> <ref>PMID:17420247</ref> <ref>PMID:8248235</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression of LONP1 promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Despite the importance of LONP1 in human biology and disease, very few LONP1 inhibitors have been described in the literature. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. Our efforts led to several nanomolar LONP1 inhibitors with little to no activity against the 20S proteasome that serve as tool compounds to investigate LONP1 biology. | ||
| + | |||
| + | Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology.,Kingsley LJ, He X, McNeill M, Nelson J, Nikulin V, Ma Z, Lu W, Zhou VW, Manuia M, Kreusch A, Gao MY, Witmer D, Vaillancourt MT, Lu M, Greenblatt S, Lee C, Vashisht A, Bender S, Spraggon G, Michellys PY, Jia Y, Haling JR, Lelais G J Med Chem. 2021 Apr 6. doi: 10.1021/acs.jmedchem.0c02152. PMID:33821636<ref>PMID:33821636</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6wys" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Endopeptidase La]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Lee | + | [[Category: Lee, C C]] |
| - | [[Category: Spraggon G]] | + | [[Category: Spraggon, G]] |
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Proteolytic domain]] | ||
Revision as of 08:28, 21 April 2021
Lon protease proteolytic domain
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