Effects of Mutations on Structure–Function Relationships of Matrix Metalloproteinase-1

Singh, Warispreet, Fields, Gregg, Christov, Christo and Karabencheva-Christova, Tatyana (2016) Effects of Mutations on Structure–Function Relationships of Matrix Metalloproteinase-1. International Journal of Molecular Sciences, 17 (10). p. 1727. ISSN 1422-0067

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Abstract

Matrix metalloproteinase-1 (MMP-1) is one of the most widely studied enzymes involved in collagen degradation. Mutations of specific residues in the MMP-1 hemopexin-like (HPX) domain have been shown to modulate activity of the MMP-1 catalytic (CAT) domain. In order to reveal the structural and conformational effects of such mutations, a molecular dynamics (MD) study was performed of in silico mutated residues in the X-ray crystallographic structure of MMP-1 complexed with a collagen-model triple-helical peptide (THP). The results indicate an important role of the mutated residues in MMP-1 interactions with the THP and communication between the CAT and the HPX domains. Each mutation has a distinct impact on the correlated motions in the MMP-1•THP. An increased collagenase activity corresponded to the appearance of a unique anti-correlated motion and decreased correlated motions, while decreased collagenase activity corresponded both to increased and decreased anti-correlated motions.

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