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Background:The human lysosomal protease cathepsin A requires proteolytic activation. Results: The crystal structure of mature and active cathepsin A reveals its mechanism of activation. Conclusion: Removal of a 3.3-kDa peptide (by unidentified proteases) allows substrate access to the active site. Significance: The results revise a 2-decades-old model of cathepsin A activation by proteolysis and subsequent conformational change.

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