PMID: 9659384Jul 11, 1998Paper

Purification and characterisation of a tripeptidyl aminopeptidase I from rat spleen

Biochimica Et Biophysica Acta
D Vines, M J Warburton

Abstract

A tripeptidyl aminopeptidase I with an M(r) of 47,000 Da has been purified from rat spleen. The N-terminal sequence of the enzyme and internal sequences did not resemble that of any known protein. The enzyme cleaves tripeptides from synthetic substrates provided that the N-terminus is unsubstituted and the amino acid in the P1 position is not charged. The enzyme also cleaves small peptides (angiotensin II and glucagon) releasing tripeptides but does not appear to demonstrate any preference for amino acids on either side of the cleavage site. The enzyme had maximum activity at pH 4 but was unstable above pH 7. Rat spleen tripeptidyl peptidase I was not inhibited by classical inhibitors of serine, cysteine, aspartate or metalloproteinases. The peptidase was potently inhibited by a series of substrate-based tripeptidyl chloromethyl ketones (Ki's of 10(-6)-10(-8) M). Inhibition was rapid and reversible. This mode of inhibition is different to the interaction between chloromethyl ketones and cysteine or serine peptidases. These tripeptidyl chloromethyl ketones were also inhibitors of bone resorption using an in vitro assay suggesting that a tripeptidyl peptidase is involved in the degradation of bone matrix proteins.

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Citations

Apr 18, 2000·Experimental Gerontology·A M Cuervo, J F Dice
Feb 28, 2009·The Journal of Biological Chemistry·Hélène AutefageNathalie Andrieu-Abadie
Oct 23, 2002·Archives of Histology and Cytology·Masato KoikeYasuo Uchiyama
May 17, 2011·Experimental Gerontology·Zongli LiKewu Huang
Feb 1, 2015·Acta histochemica·Dimitrinka Atanasova, Nikolai Lazarov
Jul 15, 2006·Biochimica Et Biophysica Acta·Aija KyttäläSandra L Hofmann
Sep 13, 2011·Journal of Agricultural and Food Chemistry·Jia-Shin LinChao-Hung Kao
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Jul 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mario A Cabrera-SalazarMarco A Passini
Aug 10, 2006·Biological Chemistry·Adam A Golabek, Elizabeth Kida
Jun 20, 2006·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Robert SteinfeldJutta Gärtner
May 15, 2004·The Journal of Biological Chemistry·Adam A GolabekElizabeth Kida
Dec 8, 2004·The Journal of Biological Chemistry·Adam A GolabekElizabeth Kida
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Mar 14, 2001·Journal of Neuropathology and Experimental Neurology·E KidaK E Wisniewski

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