6r99
From Proteopedia
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(New page: '''Unreleased structure''' The entry 6r99 is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of Human CLN protein 5 (Ceroid Lipofuscinosis Neuronal Protein 5)== | |
| + | <StructureSection load='6r99' size='340' side='right'caption='[[6r99]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6r99]] 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=6R99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R99 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6r99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r99 OCA], [https://pdbe.org/6r99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r99 RCSB], [https://www.ebi.ac.uk/pdbsum/6r99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r99 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/A0A024R644_HUMAN A0A024R644_HUMAN]] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Genetic CLN5 variants are associated with childhood neurodegeneration and Alzheimer's disease; however, the molecular function of ceroid lipofuscinosis neuronal protein 5 (Cln5) is unknown. We solved the Cln5 crystal structure and identified a region homologous to the catalytic domain of members of the N1pC/P60 superfamily of papain-like enzymes. However, we observed no protease activity for Cln5; and instead, we discovered that Cln5 and structurally related PPPDE1 and PPPDE2 have efficient cysteine palmitoyl thioesterase (S-depalmitoylation) activity using fluorescent substrates. Mutational analysis revealed that the predicted catalytic residues histidine-166 and cysteine-280 are critical for Cln5 thioesterase activity, uncovering a new cysteine-based catalytic mechanism for S-depalmitoylation enzymes. Last, we found that Cln5-deficient neuronal progenitor cells showed reduced thioesterase activity, confirming live cell function of Cln5 in setting S-depalmitoylation levels. Our results provide new insight into the function of Cln5, emphasize the importance of S-depalmitoylation in neuronal homeostasis, and disclose a new, unexpected enzymatic function for the N1pC/P60 superfamily of proteins. | ||
| - | + | Cln5 represents a new type of cysteine-based S-depalmitoylase linked to neurodegeneration.,Luebben AV, Bender D, Becker S, Crowther LM, Erven I, Hofmann K, Soding J, Klemp H, Bellotti C, Stauble A, Qiu T, Kathayat RS, Dickinson BC, Gartner J, Sheldrick GM, Kratzner R, Steinfeld R Sci Adv. 2022 Apr 15;8(15):eabj8633. doi: 10.1126/sciadv.abj8633. Epub 2022 Apr, 15. PMID:35427157<ref>PMID:35427157</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6r99" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Luebben AV]] | ||
| + | [[Category: Sheldrick GM]] | ||
Current revision
Crystal Structure of Human CLN protein 5 (Ceroid Lipofuscinosis Neuronal Protein 5)
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