Karagiannis2004_CollagenIproteolysis

This a model from the article:
A theoretical model of type I collagen proteolysis by matrix metalloproteinase
(MMP) 2 and membrane type 1 MMP in the presence of tissue inhibitor of
metalloproteinase 2.

Karagiannis ED, Popel AS. J Biol Chem
2004 Sep 10;279(37):39105-14 15252025
,
Abstract:

One well documented family of enzymes responsible for the proteolytic processes
that occur in the extracellular matrix is the soluble and membrane-associated
matrix metalloproteinases. Here we present the first theoretical model of the
biochemical network describing the proteolysis of collagen I by matrix
metalloproteinases 2 (MMP2) and membrane type 1 matrix metalloproteinases
(MT1-MMP) in the presence of the tissue inhibitor of metalloproteinases 2
(TIMP2) in a bulk, cell-free, well stirred environment. The model can serve as a
tool for describing quantitatively the activation of the MMP2 proenzyme
(pro-MMP2), the ectodomain shedding of MT1-MMP, and the collagenolysis arising
from both of the enzymes. We show that pro-MMP2 activation, a process that
involves a trimer formation of the proenzyme with TIMP2 and MT1-MMP, is
suppressed at high inhibitor levels and paradoxically attains maximum only at
intermediate TIMP2 concentrations. We also calculate the conditions for which
pro-MMP2 activation is maximal. Furthermore we demonstrate that the ectodomain
shedding of MT1-MMP can serve as a mechanism controlling the MT1-MMP
availability and therefore the pro-MMP2 activation. Finally the proteolytic
synergism of MMP2 and MT1-MMP is introduced and described quantitatively. The
model provides us a tool to determine the conditions under which the synergism
is optimized. Our approach is the first step toward a more complete description
of the proteolytic processes that occur in the extracellular matrix and include
a wider spectrum of enzymes and substrates as well as naturally occurring or
artificial inhibitors.
This model was taken from the CellML repository
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The original model was:
Karagiannis ED, Popel AS. (2004) - version01

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