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Ser475, Glu272, Asp276, Asp327, and Asp360 are involved in catalytic activity of human tripeptidyl‐peptidase I
Author(s) -
Walus Mariusz,
Kida Elizabeth,
Wisniewski Krystyna E.,
Golabek Adam A.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.01.035
Subject(s) - biochemistry , tripeptide , enzyme , serine , chemistry , aspartic acid , amino acid , biology
Tripeptidyl‐peptidase I (TPP I) is a lysosomal aminopeptidase that sequentially removes tripeptides from small polypeptides and also shows a minor endoprotease activity. Mutations in TPP I are associated with a fatal lysosomal storage disorder – the classic late‐infantile form of neuronal ceroid lipofuscinoses. In the present study, we analyzed the catalytic mechanism of the human enzyme by using a site‐directed mutagenesis. We demonstrate that apart from previously identified Ser 475 and Asp 360 , also Glu 272 , Asp 276 , and Asp 327 are important for catalytic activity of the enzyme. Involvement of serine, glutamic acid, and aspartic acid in the catalytic reaction validates the idea, formulated on the basis of significant amino acid sequence homology and inhibition studies, that TPP I is the first mammalian representative of a growing family of serine‐carboxyl peptidases.