MMP20

Matrix metalloproteinase 20 (MMP-20), also known as enamelysin, is a zinc-dependent endopeptidase of the matrix metalloproteinase (MMP) family. In humans, MMP-20 is expressed by ameloblasts during tooth development and is secreted into the enamel organ, where it participates in enamel matrix remodeling during the maturation stage.

Functionally, MMP-20 cleaves enamel matrix proteins, including amelogenin, ameloblastin, and enamelin, helping to remove and reorganize the protein-rich matrix that guides enamel mineralization. Proper proteolysis by MMP-20 allows hydroxyapatite crystal growth and enamel hardening.

Biochemically, MMP-20 is synthesized as an inactive zymogen with a propeptide. Activation involves removal of the prodomain to expose a catalytic zinc-binding site containing the HExGHxxGxxH motif. The enzyme has a catalytic domain and a C-terminal hemopexin-like domain that mediates substrate interactions and influences specificity. It is secreted into the extracellular enamel matrix and can be regulated by tissue inhibitors of metalloproteinases (TIMPs).

Genetic and clinical significance: Pathogenic variants in MMP-20 have been associated with amelogenesis imperfecta, a disorder of enamel formation. In affected individuals, enamel can be hypoplastic or hypomineralized, with reduced hardness and increased wear. Most reported cases follow an autosomal recessive pattern of inheritance.

Research and models: Studies in Mmp-20 knockout mice show enamel defects consistent with impaired enamel maturation, reinforcing the enzyme’s essential role in tooth development.