Conformation and Domain Movement Analysis of Human Matrix Metalloproteinase-2: Role of Associated Zn 2+ and Ca 2+ Ions
Matrix metaloproteinase-2 (MMP-2) is an extracellular Zn protease specific to type I and IV collagens. Its expression is associated with several inflammatory, degenerative, and malignant diseases. Conformational properties, domain movements, and interactions between MMP-2 and its associated metal io...
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Published in | International journal of molecular sciences Vol. 20; no. 17 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
27.08.2019
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Subjects | |
Online Access | Get full text |
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Summary: | Matrix metaloproteinase-2 (MMP-2) is an extracellular Zn
protease specific to type I and IV collagens. Its expression is associated with several inflammatory, degenerative, and malignant diseases. Conformational properties, domain movements, and interactions between MMP-2 and its associated metal ions were characterized using a 1.0 µs molecular dynamics simulation. Dihedral principle component analysis revealed ten families of conformations with the greatest degree of variability occurring in the link region connecting the catalytic and hemopexin domains. Dynamic cross-correlation analysis indicated domain movements corresponding to the opening and closing of the hemopexin domain in relation to the fibronectin and catalytic domains facilitated by the link region. Interaction energies were calculated using the molecular mechanics Poisson Boltzman surface area-interaction entropy (MMPBSA-IE) analysis method and revealed strong binding energies for the catalytic Zn
ion 1, Ca
ion 1, and Ca
ion 3 with significant conformational stability at the binding sites of Zn
ion 1 and Ca
ion 1. Ca
ion 2 diffuses freely away from its crystallographically defined binding site. Zn
ion 2 plays a minor role in conformational stability of the catalytic domain while Ca
ion 3 is strongly attracted to the highly electronegative sidechains of the Asp residues around the central β-sheet core of the hemopexin domain; however, the interacting residue sidechain carboxyl groups are outside of Ca
ion 3's coordination sphere. |
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ISSN: | 1422-0067 |