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			PubMed Journals: J Biol Chem

  Source:		PMID: 11115496


    		J Biol Chem. 2001 Mar 16;276(11):8118-24.
     		Epub 2000 Dec 13.

			Identification of internal autoproteolytic
			cleavage sites within the prosegments of
			recombinant procathepsin B and procathepsin S.
			Contribution of a plausible unimolecular
			autoproteolytic event for the processing
			of zymogens belonging to the papain family.

			Quraishi O(1), Storer AC.

			Author Information
			(1) Protein Engineering Network of Centres
			of Excellence and Department of Biochemistry,
			McGill University, Montreal, Quebec H3G
			1Y6, Canada.

			The steps involved in the maturation of
			proenzymes belonging to the papain family
			of cysteine proteases have been difficult
			to characterize. Intermolecular processing
			at or near the pro/mature junction, due
			either to the catalytic activity of active
			enzyme or to exogeneous proteases, has been
			well documented for this family of proenzymes.
			In addition, kinetic studies are suggestive
			of a slow unimolecular mechanism of autoactivation
			which is independent of proenzyme concentration.
			However, inspection of the recently determined
			x-ray crystal structures does not support
			this evidence. This is due primarily to
			the extensive distances between the catalytic
			thiolate-imidazolium ion pair and the putative
			site of proteolysis near the pro/mature
			junction required to form mature protein.
			Furthermore, the prosegments for this family
			of precursors have been shown to bind through
			the substrate binding clefts in a direction
			opposite to that expected for natural substrates.
			We report, using cystatin C- and N-terminal
			sequencing, the identification of autoproteolytic
			intermediates of processing in vitro for
			purified recombinant procathepsin B and procathepsin S.
			Inspection of the x-ray crystal structures
			reported to date indicates that these reactions
			occur within a segment of the proregion
			which binds through the substrate binding
			clefts of the enzymes, thus suggesting that
			these reactions are occurring as unimolecular
			processes.

			DOI: 10.1074/jbc.M005851200 PMID: 11115496
			[Indexed for MEDLINE]

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