Molecular Modeling and Comparison of Three-Dimensional Structures of Enamelysin: a Matrix Metalloproteinase
Presenter: Debra T. Hsiung
Health Careers High School
摘要：
DNA encoding a previously unknown proteinase named enamelysin was recently isolated and characterized. Enamelysin is produced in developing teeth, where it cleaves precursor proteins into their active forms. Mutations in the enamelysin gene are believed to cause the inherited disease amelogenesis imperfecta, or AI. Enamelysin is classified as a matrix metalloproteinase and designated MMP-20. Since enamelysin is a novel protein, not much is known about its structure and function. It was hypothesized that the 3-D structure of MMP-20 is very similar to that of other MMPs and its form can be closely approximated by modeling it after the crystal structures of its closest relatives. An inactive model of MMP-20 based upon MMP-3 was successfully constructed in the previous year of this study using computer modeling techniques. An active (truncated) model of the entire MMP-20 protein based upon MMP-1 was produced this year and used to investigate the structure and function of enamelysin by comparing it with the inactive model. Phylogenetic, temperature, and homology analyses suggest that the computer models closely approximate the actual enamelysin structure. Examination of the models indicates that: the secondary structure of the hemopexin domain includes a four-bladed beta propeller, the structures of the protein's catalytic domain before and after activation are nearly identical, and the protein is activated by a mechanism called a cysteine switch. These results demonstrate that computer molecular modeling can be used to gain a better understanding of the structure and function of enamelysin.