Catalytic Residues and Substrate Specificity of Recombinant Human Tripeptidyl Peptidase I (CLN2)

[subscript m] value for this substrate was 40 times higher than that for Ala-Ala-Phe-MCA. Coupled with other data, these results strongly suggest that the substrate-binding cleft of TPP-I is composed of only six subsites (S₃-S₃'). TPP-I prefers bulky and hydrophobic amino acid residues at the P...

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Bibliographic Details
Published in:Journal of biochemistry (Tokyo) 2005-08, Vol.138 (2), p.127-134
Main Authors: Oyama, Hiroshi, Fujisawa, Tomoko, Suzuki, Takao, Dunn, Ben M, Wlodawer, Alexander, Oda, Kohei
Format: Article
Language:English
Subjects:
Aminopeptidases
Animals
Bombyx
Catalytic Domain
classical late-infantile neuronal ceroid lipofuscinosis
CLN2
CPd
cysteine proteinase gene deleted
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Endopeptidases
Humans
Kinetics
Mutagenesis, Site-Directed
mutated protein
mutein
neurodegenerative disease
Peptide Hydrolases - genetics
Peptide Hydrolases - metabolism
Peptides - metabolism
Recombinant Proteins
sedolisin
Serine Proteases
serine-carboxyl proteinase
Substrate Specificity
TPP-I
tripeptidyl peptidase I
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Description
Summary:[subscript m] value for this substrate was 40 times higher than that for Ala-Ala-Phe-MCA. Coupled with other data, these results strongly suggest that the substrate-binding cleft of TPP-I is composed of only six subsites (S₃-S₃'). TPP-I prefers bulky and hydrophobic amino acid residues at the P₁ position and Ala, Arg, or Asp at the P₂ position. Hydrophilic interactions at the S₂ subsite are necessary for TPP-I, and this feature is unique among serine-carboxyl proteinases. TPP-I might have evolved from an ancestral gene in order to cleave, in cooperation with cathepsins, useless proteins in the lysosomal compartment.
ISSN:0021-924X
1756-2651
DOI:10.1093/jb/mvi110