Development of Chemical Tools to Monitor and Control Isoaspartyl Peptide Methyltransferase Activity

Yusuke Kimura, Toru Komatsu, Kouichi Yanagi, Kenjiro Hanaoka, Tasuku Ueno, Takuya Terai, Hirotatsu Kojima, Takayoshi Okabe, Tetsuo Nagano, Yasuteru Urano

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

We have established a coupled assay system targeting protein l-isoaspartyl methyltransferase (PIMT), a key enzyme in the metabolism of isoaspartyl peptides and proteins. The system utilizes a fluorogenic peptide probe containing an isoaspartyl residue at the P1′ position of the caspase-3 recognition sequence. Following PIMT-catalyzed methyl transfer reaction, the methylated probe is specifically cleaved by caspase-3 to give fluorescence activation. High-throughput screening of our chemical library with this assay system identified PIMT inhibitors that may be useful as leads in the design of chemical probes for controlling PIMT activity.

Original languageEnglish
Pages (from-to)153-157
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number1
DOIs
Publication statusPublished - 2017 Jan 2
Externally publishedYes

Keywords

  • activity-based probes
  • enzymes
  • fluorogenic probes
  • inhibitors
  • methyltransferases

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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