Identification of substrate sequences for membrane type-1 matrix metalloproteinase using bacteriophage peptide display library

Shuichi Ohkubo, Kazutaka Miyadera, Yoshikazu Sugimoto, Ken Ichi Matsuo, Konstanty Wierzba, Yuji Yamada

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Abstract

Membrane type-1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of progelatinase A (proMMP-2) which is associated with tumor invasion and metastasis, and also known to have an ability to digest extracellular matrix components. To clarify substrate specificity of MT1-MMP, we have searched for amino acid sequences cleaved by this protease using the hexamer substrate phage library consisting of a large number of randomized amino acid sequences. The consensus substrate sequences for MT1-MMP were deduced from the selected clones and appeared to be P-X-G/P-L at the P3-P1' sites. Peptide cleavage assay revealed that MT1-MMP preferentially digested a synthetic substrate containing Pro of the P1 position compared to that being substituted with Gly. Our results may have an important implication to identifying new target proteins for MT1-MMP and leading to the design of its selective inhibitors suitable for cancer chemotherapy.

Original languageEnglish
Pages (from-to)308-313
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume266
Issue number2
DOIs
Publication statusPublished - 1999 Dec 20
Externally publishedYes

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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