title: Identification of substrate sequences for membrane type-1 matrix metalloproteinase using bacteriophage peptide display library.
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 acids 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.
authors.affiliation: Hanno Research Center, Taiho Pharmaceutical Company, Ltd., 1-27 Misugi-dai, Hanno, Saitama, 357-8527, Japan. s-ohkubo@taiho.co.jp
authors.forename: S
authors.initials: S
authors.lastname: Ohkubo
authors.forename: K
authors.initials: K
authors.lastname: Miyadera
authors.forename: Y
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: K
authors.initials: K
authors.lastname: Matsuo
authors.forename: K
authors.initials: K
authors.lastname: Wierzba
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D001435:Bacteriophages; D003114:Colony-Forming Units Assay; D016384:Consensus Sequence; D004926:Escherichia coli; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D019151:Peptide Library; D010455:Peptides; D020781:Matrix Metalloproteinase 1