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

Research output: Contribution to journalArticle

44 Citations (Scopus)

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

Fingerprint

Matrix Metalloproteinase 14
Peptide Library
Bacteriophages
Display devices
Peptides
Substrates
Amino Acid Sequence
Amino Acids
Chemotherapy
Consensus Sequence
Substrate Specificity
Extracellular Matrix
Tumors
Assays
Neoplasms
Peptide Hydrolases
Clone Cells
Chemical activation
Neoplasm Metastasis
Drug Therapy

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Identification of substrate sequences for membrane type-1 matrix metalloproteinase using bacteriophage peptide display library. / Ohkubo, Shuichi; Miyadera, Kazutaka; Sugimoto, Yoshikazu; Matsuo, Ken Ichi; Wierzba, Konstanty; Yamada, Yuji.

In: Biochemical and Biophysical Research Communications, Vol. 266, No. 2, 20.12.1999, p. 308-313.

Research output: Contribution to journalArticle

Ohkubo, Shuichi ; Miyadera, Kazutaka ; Sugimoto, Yoshikazu ; Matsuo, Ken Ichi ; Wierzba, Konstanty ; Yamada, Yuji. / Identification of substrate sequences for membrane type-1 matrix metalloproteinase using bacteriophage peptide display library. In: Biochemical and Biophysical Research Communications. 1999 ; Vol. 266, No. 2. pp. 308-313.
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