Title : Structure of human
dipeptidyl peptidase I (
cathepsin C ): exclusion
domain added to an
endopeptidase framework creates the machine for activation of granular
serine proteases
Abstract :
- Dipeptidyl peptidase I ( DPPI ) or cathepsin C is the physiological activator of groups of serine proteases from immune and inflammatory cells vital for defense of an organism
- The structure presented shows how an additional domain transforms the framework of a papain-like endopeptidase into a robust oligomeric protease-processing enzyme
- The tetrahedral arrangement of the active sites exposed to solvent allows approach of proteins in their native state; the massive body of the exclusion domain fastened within the tetrahedral framework excludes approach of a polypeptide chain apart from its termini; and the carboxylic group of Asp1 positions the N-terminal amino group of the substrate
- Based on a structural comparison and interactions within the active site cleft, it is suggested that the exclusion domain originates from a metallo-protease inhibitor
- The location of missense mutations, characterized in people suffering from Haim-Munk and Papillon-Lefevre syndromes, suggests how they disrupt the fold and function of the enzyme
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Output(Part-Of) (sent_index,
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*Output_Site_Fusion* (sent_index,
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