Generation of an angiostatin-like fragment from plasminogen by stromelysin-1 (MMP-3)

Biochemistry. 1998 Apr 7;37(14):4699-702. doi: 10.1021/bi9731798.


Matrix metalloproteinase-3 (MP-3 or stromelysin-1) specifically hydrolyzes the Glu59-Asn60, Pro447-Val448, and Pro544-Ser545 peptide bonds in plasminogen, yielding a 55 kDa NH2-terminal angiostatin-like domain (comprising kringles 1-4), a 14 kDa domain comprising kringle 5, and a 30 kDa domain comprising the serine proteinases domain. The conversion is completely abolished in the presence of the MMP inhibitors EDTA or 1,10-phenanthroline. Biospecific interactions analysis indicates that binding of proMMP-3 and MMP-3 to plasminogen occurs with comparable affinity (KA of 4.7 x 10(6) and 4.1 x 10(6) M-1, respectively) and is mediated via the miniplasminogen moiety (kringle 5 plus the proteinase domain) and via the catalytic domain of MMP-3. Thus, proteolytic cleavage of plasminogen by MMP-3 generates angiostatin-like fragments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiostatins
  • Humans
  • Hydrolysis
  • Matrix Metalloproteinase 3 / chemistry*
  • Matrix Metalloproteinase 3 / metabolism
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Plasminogen / chemistry*
  • Plasminogen / metabolism
  • Protein Binding
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism


  • Peptide Fragments
  • Recombinant Proteins
  • Angiostatins
  • Plasminogen
  • Matrix Metalloproteinase 3