Back to Search
Start Over
The specificity of lysosomal tripeptidyl peptidase-I determined by its action on angiotensin-II analogues.
- Source :
-
FEBS letters [FEBS Lett] 2001 Jul 06; Vol. 500 (3), pp. 145-8. - Publication Year :
- 2001
-
Abstract
- Tripeptidyl peptidase-I (TPP-I) is a lysosomal peptidase which cleaves tripeptides from the N-terminus of peptides. The function of the enzyme is unclear but its importance is demonstrated by the fact that mutations in TPP-I are responsible for late infantile neuronal ceroid lipofuscinosis, a lethal lysosomal storage disease. As a step towards identifying its natural substrates, we have used a series of synthetic peptides, based on angiotensin-II, to explore the effects of peptide chain length and the effects of amino acid substitutions at the P1 and P1' positions on the rate of catalysis. With the exception of angiotensin-(1-8) (angiotensin-II), which is a relatively poor substrate for TPP-I, the rate of catalysis increases with increasing chain length. K(cat)/K(m) values increase 50-fold between angiotensin-(1-5) and angiotensin-(1-14). TPP-I shows little specificity for the nature of the amino acids in the P1 and P1' positions, K(cat)/K(m) values varying only 5-fold for a range of substitutions. However, Pro or Lys in the P1 position and Pro in the P1' positions are incompatible with TPP-I activity. These observations suggest that TPP-I is a non-specific, but essential, peptidase involved in the latter stages of lysosomal protein degradation.
- Subjects :
- Amino Acid Substitution
Aminopeptidases
Angiotensin II analogs & derivatives
Angiotensin II drug effects
Animals
Catalysis
Chromatography, High Pressure Liquid
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Endopeptidases pharmacology
Hydrogen-Ion Concentration
Neuronal Ceroid-Lipofuscinoses enzymology
Peptides chemistry
Peptides drug effects
Serine Proteases
Structure-Activity Relationship
Substrate Specificity physiology
Swine
Tripeptidyl-Peptidase 1
Angiotensin II chemistry
Endopeptidases chemistry
Lysosomes enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-5793
- Volume :
- 500
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- FEBS letters
- Publication Type :
- Academic Journal
- Accession number :
- 11445074
- Full Text :
- https://doi.org/10.1016/s0014-5793(01)02608-4