ADAM38 Activators

Chemical activators of ADAM20 include a variety of compounds that engage with the enzyme to enhance its proteolytic activity. Zinc acetate contributes to this process by providing zinc ions that bind to the active site of ADAM20, maintaining structural integrity vital for its catalytic function. Similarly, manganese(II) sulfate supplies manganese ions which act as cofactors essential for the protease's enzymatic action. Copper(II) sulfate's contribution is through copper ions interacting with the metalloprotease domain of ADAM20, which is crucial for its function. Magnesium chloride and calcium chloride also participate by providing magnesium and calcium ions, respectively, which help stabilize the enzyme's structure and ensure proper substrate binding.

Further activation of ADAM20 is facilitated by compounds that induce phosphorylation or other post-translational modifications. Sodium orthovanadate activates ADAM20 by inhibiting protein tyrosine phosphatases, leading to a higher phosphorylation state of proteins that regulate the metallopeptidase. Phorbol 12-myristate (PMA) activates protein kinase C, which in turn can phosphorylate ADAM20, while forskolin stimulates adenylate cyclase, increasing cAMP levels and activating protein kinase A, which may also target ADAM20 for phosphorylation. Hydrogen peroxide triggers oxidative mechanisms that can induce changes enhancing ADAM20's activity. Sodium nitroprusside, which releases nitric oxide, can lead to S-nitrosylation of ADAM20, modifying its interaction with substrates or regulatory proteins. Cobalt(II) chloride and nickel(II) sulfate can activate ADAM20 by providing cobalt and nickel ions, respectively, that may serve as alternative cofactors or bind to the metalloprotease domain, potentially boosting the enzyme's proteolytic efficiency.