Role of basic amino acids in the cleavage of synthetic peptide substrates by mitochondrial processing peptidase

Myeong Cheol Song, Kunitoshi Shimokata, Sakae Kitada, Tadashi Ogishima, Akio Ito

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31 Citations (Scopus)

Abstract

Our recent experiments using model peptides of rat malate dehydrogenase (MDH) indicated that a proximal arginine and a distal basic amino acid are important for processing by mitochondrial processing peptidase (MPP). To elucidate if the recognition elements apply to other precursor proteins, we analyzed cleavage of model peptides of human ornithine aminotransferase (OAT). Purified peptidase cleaved peptides that corresponded to N-terminal 1-25 and 3-25 at the correct site (Gly17-Val18) at nearly equal rates. Replacement of Arg15 (-2 position) with lysine or alanine reduced the processing efficiency by 95- and 380-fold, respectively. Either deletion from Met1 to Arg10 or replacement of the basic amino acids between them decreased the processing efficiency considerably. A peptide containing Arg7 in addition to Lys4 and Arg10 was more effective than the control peptide. However, a peptide with one and two consecutive basic amino acids in the distal region had a processing efficiency close to the control peptide. These results indicated that processing of OAT was enhanced by an increase in the number of basic amino acids with a suitable distance between them. In other respects, the processing signal of OAT was essentially the same as that of MDH.

Original languageEnglish
Pages (from-to)1163-1166
Number of pages4
JournalJournal of biochemistry
Volume120
Issue number6
DOIs
Publication statusPublished - Jan 1 1996

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

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