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Activation mechanisms of the precursors of matrix metalloproteinases 1, 2 and 3

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  • H Nagase, Denmark
  • K Suzuki, Denmark
  • T Morodomi, Denmark
  • J J Enghild
  • G Salvesen, Denmark
  • Interdisciplinary Nanoscience Center
  • Department of Molecular Biology
The zymogens of matrix metalloproteinase 1 (MMP-1: tissue collagenase), MMP-2 (gelatinase/type IV collagenase) and MMP-3 (stromelysin) were purified from the culture medium of human rheumatoid synovial fibroblasts and the mechanisms of activation of each zymogen by proteinases and 4-aminophenylmercuric acetate (APMA) were studied by kinetic and sequence analyses. The treatment of proMMP-1 (M(r) = 52,000) with proteinases or APMA converted the zymogen to M(r) = 43,000, but it exhibited only 14-25% of the maximal activity. Incubation of a partially active MMP-1 with MMP-3 resulted in rapid, full activation by generating the 41,000-M(r) MMP-1 with Phe81 as the NH2-terminus. MMP-3 directly activated proMMP-1 by cleaving the Gln80-Phe81 bond, but this reaction was extremely slow, indicating that the Gln80-Phe81 bond is not readily available to MMP-3 in the native proMMP-1 molecule. ProMMP-2 (M(r) = 72,000) was activated only by APMA, but not by proteinases. The activation by APMA was rapid and generated an active MMP-2 of M(r) 68,000, but the enzymic activity declined rapidly after activation by autolysis. The NH2-terminal sequence analysis of active MMP-2 indicated that the Asn80-Tyr81 bond was cleaved upon APMA treatment. In contrast, proMMP-3 (M(r) = 57,000) was activated by a variety of proteinases with different specificities. The initial attacks of these proteinases are on a stretch of highly charged groups at the position 34-39 in the propeptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Original languageEnglish
JournalMatrix (Stuttgart, Germany). Supplement
Pages (from-to)237-44
Number of pages7
Publication statusPublished - 1992

    Research areas

  • Amino Acid Sequence, Arthritis, Rheumatoid, Collagenases, Endopeptidases, Enzyme Activation, Enzyme Precursors, Fibroblasts, Humans, Matrix Metalloproteinase 1, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Metalloendopeptidases, Molecular Sequence Data, Molecular Weight, Phenylmercuric Acetate, Sequence Alignment, Synovial Fluid

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