Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed

Science. 1999 Jun 4;284(5420):1667-70. doi: 10.1126/science.284.5420.1667.

Abstract

Matrix metalloproteinases (MMPs) catalyze extracellular matrix degradation. Control of their activity is a promising target for therapy of diseases characterized by abnormal connective tissue turnover. MMPs are expressed as latent proenzymes that are activated by proteolytic cleavage that triggers a conformational change in the propeptide (cysteine switch). The structure of proMMP-2 reveals how the propeptide shields the catalytic cleft and that the cysteine switch may operate through cleavage of loops essential for propeptide stability.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Enzyme Activation
  • Enzyme Precursors / chemistry*
  • Enzyme Precursors / metabolism
  • Fibronectins / chemistry
  • Gelatinases / chemistry*
  • Gelatinases / metabolism
  • Hemopexin / chemistry
  • Humans
  • Hydrogen Bonding
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / chemistry*
  • Metalloendopeptidases / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary

Substances

  • Enzyme Precursors
  • Fibronectins
  • Hemopexin
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2

Associated data

  • PDB/1CK7