Mammalian pitrilysin: Substrate specificity and mitochondrial targeting

K. Martin Chow, O. Gakh, I. C. Payne, Maria Aparecida Juliano, Luiz Juliano, G. Isaya, Louis B. Hersh

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The substrate specificity of the mitochondrial metallopeptidase proteinase 1 (MP1) was investigated and its mitochondrial targeting signal identified. The substrate specificity of MP1 was examined with physiological peptides as substrates. Although the enzyme exhibits broad substrate specificity, there is a trend for peptides containing 13 or more residues to exhibit K m values of 2 μM or less. Three of four peptides containing 11 or fewer residues exhibited K m values above 10 μM. Similarly, peptides containing 13 or more residues exhibited k cat values below 10 min -1, while three of four peptides containing 11 or fewer residues exhibited k cat values above 30 min -1. Many of the peptide cleavage sites of MP1 resemble that of the mitochondrial processing protease (MPP); however, MP1 does not process the precursor form of citrate synthase. The enzyme, however, does cleave the released prepeptide from precitrate synthase. A mitochondria local zation was shown in MP1 transfected NT2 and HepG2 cells. Deletion of the N-terminal 15 amino acids caused MP1 to be mislocalized to the cytoplasm and nucleus. Furthermore, when fused to green flourescent protein, this 15-amino acid N-terminal sequence directed the fusion protein to the mitochondria.

Original languageEnglish (US)
Pages (from-to)2868-2877
Number of pages10
JournalBiochemistry
Volume48
Issue number13
DOIs
StatePublished - Apr 7 2009

ASJC Scopus subject areas

  • Biochemistry

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    Chow, K. M., Gakh, O., Payne, I. C., Juliano, M. A., Juliano, L., Isaya, G., & Hersh, L. B. (2009). Mammalian pitrilysin: Substrate specificity and mitochondrial targeting. Biochemistry, 48(13), 2868-2877. https://doi.org/10.1021/bi8016125