4i04: Difference between revisions
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== | ==Structure of zymogen of cathepsin B1 from Schistosoma mansoni== | ||
[[4i04]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I04 OCA]. | <StructureSection load='4i04' size='340' side='right'caption='[[4i04]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
[[ | == Structural highlights == | ||
[[ | <table><tr><td colspan='2'>[[4i04]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I04 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]] 1.95Å</td></tr> | ||
[[Category: | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
[[Category: | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4i04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i04 OCA], [https://pdbe.org/4i04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i04 RCSB], [https://www.ebi.ac.uk/pdbsum/4i04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i04 ProSAT]</span></td></tr> | ||
[[Category: | </table> | ||
[[Category: | == Function == | ||
[[Category: | [https://www.uniprot.org/uniprot/Q8MNY2_SCHMA Q8MNY2_SCHMA] | ||
[[Category: | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | |||
Cathepsin B1 (SmCB1) is a digestive protease of the parasitic blood fluke Schistosoma mansoni and a drug target for the treatment of schistosomiasis, a disease that afflicts over 200 million people. SmCB1 is synthesized as an inactive zymogen in which the N-terminal propeptide blocks the active site. We investigated the activation of the zymogen by which the propeptide is proteolytically removed and its regulation by sulfated polysaccharides (SPs). We determined crystal structures of three molecular forms of SmCB1 along the activation pathway: the zymogen, an activation intermediate with a partially cleaved propeptide, and the mature enzyme. We demonstrate that SPs are essential for the autocatalytic activation of SmCB1, as they interact with a specific heparin-binding domain in the propeptide. An alternative activation route is mediated by an S. mansoni asparaginyl endopeptidase (legumain) which is downregulated by SPs, indicating that SPs act as a molecular switch between both activation mechanisms. | |||
Activation route of the Schistosoma mansoni cathepsin B1 drug target: structural map with a glycosaminoglycan switch.,Jilkova A, Horn M, Rezacova P, Maresova L, Fajtova P, Brynda J, Vondrasek J, McKerrow JH, Caffrey CR, Mares M Structure. 2014 Dec 2;22(12):1786-98. doi: 10.1016/j.str.2014.09.015. Epub 2014, Nov 13. PMID:25456815<ref>PMID:25456815</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4i04" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Schistosoma mansoni]] | |||
[[Category: Brynda J]] | |||
[[Category: Horn M]] | |||
[[Category: Jilkova A]] | |||
[[Category: Mares M]] | |||
[[Category: Rezacova P]] | |||
Latest revision as of 17:11, 8 November 2023
Structure of zymogen of cathepsin B1 from Schistosoma mansoniStructure of zymogen of cathepsin B1 from Schistosoma mansoni
Structural highlights
FunctionPublication Abstract from PubMedCathepsin B1 (SmCB1) is a digestive protease of the parasitic blood fluke Schistosoma mansoni and a drug target for the treatment of schistosomiasis, a disease that afflicts over 200 million people. SmCB1 is synthesized as an inactive zymogen in which the N-terminal propeptide blocks the active site. We investigated the activation of the zymogen by which the propeptide is proteolytically removed and its regulation by sulfated polysaccharides (SPs). We determined crystal structures of three molecular forms of SmCB1 along the activation pathway: the zymogen, an activation intermediate with a partially cleaved propeptide, and the mature enzyme. We demonstrate that SPs are essential for the autocatalytic activation of SmCB1, as they interact with a specific heparin-binding domain in the propeptide. An alternative activation route is mediated by an S. mansoni asparaginyl endopeptidase (legumain) which is downregulated by SPs, indicating that SPs act as a molecular switch between both activation mechanisms. Activation route of the Schistosoma mansoni cathepsin B1 drug target: structural map with a glycosaminoglycan switch.,Jilkova A, Horn M, Rezacova P, Maresova L, Fajtova P, Brynda J, Vondrasek J, McKerrow JH, Caffrey CR, Mares M Structure. 2014 Dec 2;22(12):1786-98. doi: 10.1016/j.str.2014.09.015. Epub 2014, Nov 13. PMID:25456815[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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