TAILIEUCHUNG - Báo cáo khoa học: Autocatalytic processing of procathepsin B is triggered by proenzyme activity

Cathepsin B (EC ) and other cysteine proteases are synthesized as zymogens, which are processed to their mature forms autocatalytically or by other proteases. Autocatalytic processing was suggested to be a bimolec-ular process, whereas initiation of the processing has not yet been clarified. | Autocatalytic processing of procathepsin B is triggered by proenzyme activity Jerica Rozman Pungercar1 Dejan Caglic1 Mohammed Sajid3 Marko Dolinar2 Olga Vasiljeva1 Urska PoZgan1 DuSan Turk1 Matthew Bogyo4 Vito Turk1 and Boris Turk1 1 Department of Biochemistry and Molecular and StructuralBiology Jozef Stefan Institute Ljubljana Slovenia 2 Faculty of Chemistry and ChemicalTechnology University of Ljubljana Slovenia 3 Biochemistry and Molecular Biology Core Sandler Center for Basic Research in Parasitic Diseases University of California San Francisco CA USA 4 Department of Pathology Stanford University Schoolof Medicine CA USA Keywords autoactivation DCG-04 lysosomalcysteine protease procathepsin B processing Correspondence B. Turk Department of Biochemistry and Molecular and StructuralBiology Jozef Stefan Institute Jamova 39 1000 Ljubljana Slovenia Fax 386 1 477 3984 Tel 386 1 477 3772 E-mail These authors contributed equally to this work Received 17 September 2008 revised 13 November 2008 accepted 24 November 2008 doi Cathepsin B EC and other cysteine proteases are synthesized as zymogens which are processed to their mature forms autocatalytically or by other proteases. Autocatalytic processing was suggested to be a bimolec-ular process whereas initiation of the processing has not yet been clarified. Procathepsin B was shown by zymography to hydrolyze the synthetic substrate 7-N-benzyloxycarbonyl-L-arginyl-L-arginylamide-4-methylcoumarin Z-Arg-Arg-NH-MEC suggesting that procathepsin B is catalytically active. The activity-based probe DCG-04 which is an E-64-type inhibitor was found to label both mature cathepsin B and its zymogen confirming the zymography data. Mutation analyses in the linker region between the propeptide and the mature part revealed that autocatalytic processing of procathepsin B is largely unaffected by mutations in this region including mutations to prolines. On the basis of these .

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