title: Effects of Mutations on Structure-Function Relationships of Matrix Metalloproteinase-1.
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.
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, NE1 8ST, UK. warispreet.singh@northumbria.ac.uk.
authors.forename: Warispreet
authors.initials: W
authors.lastname: Singh
authors.affiliation: Department of Chemistry & Biochemistry, Florida Atlantic University, Jupiter, FL 33458, USA. fieldsg@fau.edu.|Department of Chemistry, The Scripps Research Institute/Scripps Florida, Jupiter, FL 33458, USA. fieldsg@fau.edu.
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Fields
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, NE1 8ST, UK. christo.christov@northumbria.ac.uk.
authors.forename: Christo Z
authors.initials: CZ
authors.lastname: Christov
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, NE1 8ST, UK. tatyana.karabencheva-christova@northumbria.ac.uk.
authors.forename: Tatyana G
authors.initials: TG
authors.lastname: Karabencheva-Christova
mesh_terms: D020134:Catalytic Domain; D003094:Collagen / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011487:Protein Conformation
chemical_list: D003094:Collagen; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: conformational flexibility; correlated motions; matrix metalloproteinase-1; molecular dynamics simulations; mutations