Title : Proteolytic activation of human cathepsin A - Kolli_2014_J.Biol.Chem_289_11592
Author(s) : Kolli N , Garman SC
Ref : Journal of Biological Chemistry , 289 :11592 , 2014
Abstract :

Galactosialidosis is a human lysosomal storage disease caused by deficiency in the multifunctional lysosomal protease cathepsin A (also known as protective protein/cathepsin A, PPCA, catA, HPP, and CTSA; EC Previous structural work on the inactive precursor human cathepsin A (zymogen) led to a two-stage model for activation, where proteolysis of a 1.6-kDa excision peptide is followed by a conformational change in a blocking peptide occluding the active site. Here we present evidence for an alternate model of activation of human cathepsin A, needing only cleavage of a 3.3-kDa excision peptide to yield full enzymatic activity, with no conformational change required. We present x-ray crystallographic, mass spectrometric, amino acid sequencing, enzymatic, and cellular data to support the cleavage-only activation model. The results clarify a longstanding question about the mechanism of cathepsin A activation and point to new avenues for the design of mechanism-based inhibitors of the enzyme.

PubMedSearch : Kolli_2014_J.Biol.Chem_289_11592
PubMedID: 24599961
Gene_locus related to this paper: human-CTSA

Related information

Gene_locus human-CTSA
Family human-CTSA    Carboxypeptidase_S10
Structure human-CTSA    Carboxypeptidase_S10    4MWS    4MWT

Citations formats

Kolli N, Garman SC (2014)
Proteolytic activation of human cathepsin A
Journal of Biological Chemistry 289 :11592

Kolli N, Garman SC (2014)
Journal of Biological Chemistry 289 :11592