4i04

Structure of zymogen of cathepsin B1 from Schistosoma mansoni

spinqualitylabelsall models 4i04, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4i04 is a 4 chain structure with sequence from Schistosoma mansoni. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8MNY2_SCHMA 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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