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Examination of matrix metalloproteinase-1 in solution: a preference for the pre-collagenolysis state.


ABSTRACT: Catalysis of collagen degradation by matrix metalloproteinase 1 (MMP-1) has been proposed to critically rely on flexibility between the catalytic (CAT) and hemopexin-like (HPX) domains. A rigorous assessment of the most readily accessed conformations in solution is required to explain the onset of substrate recognition and collagenolysis. The present study utilized paramagnetic NMR spectroscopy and small angle x-ray scattering (SAXS) to calculate the maximum occurrence (MO) of MMP-1 conformations. The MMP-1 conformations with large MO values (up to 47%) are restricted into a relatively small conformational region. All conformations with high MO values differ largely from the closed MMP-1 structures obtained by x-ray crystallography. The MO of the latter is ~20%, which represents the upper limit for the presence of this conformation in the ensemble sampled by the protein in solution. In all the high MO conformations, the CAT and HPX domains are not in tight contact, and the residues of the HPX domain reported to be responsible for the binding to the collagen triple-helix are solvent exposed. Thus, overall analysis of the highest MO conformations indicated that MMP-1 in solution was poised to interact with collagen and then could readily proceed along the steps of collagenolysis.

SUBMITTER: Cerofolini L 

PROVIDER: S-EPMC3798536 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Examination of matrix metalloproteinase-1 in solution: a preference for the pre-collagenolysis state.

Cerofolini Linda L   Fields Gregg B GB   Fragai Marco M   Geraldes Carlos F G C CFGC   Luchinat Claudio C   Parigi Giacomo G   Ravera Enrico E   Svergun Dmitri I DI   Teixeira João M C JMC  

The Journal of biological chemistry 20130911 42


Catalysis of collagen degradation by matrix metalloproteinase 1 (MMP-1) has been proposed to critically rely on flexibility between the catalytic (CAT) and hemopexin-like (HPX) domains. A rigorous assessment of the most readily accessed conformations in solution is required to explain the onset of substrate recognition and collagenolysis. The present study utilized paramagnetic NMR spectroscopy and small angle x-ray scattering (SAXS) to calculate the maximum occurrence (MO) of MMP-1 conformation  ...[more]

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