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

Warispreet Singh, Gregg Fields, Christo Christov, Tatyana Karabencheva-Christova

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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.
Original languageEnglish
Pages (from-to)1727
JournalInternational Journal of Molecular Sciences
Volume17
Issue number10
DOIs
Publication statusPublished - 14 Oct 2016

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