Metalloproteinases, Biophysics and Chemistry of

Abstract

Zinc‐dependent metalloproteases constitute a large family of enzymes, part of the proteinase superfamily. Fundamental to the structural integrity and catalytic activity of metalloproteases is the presence of both zinc and calcium ions in the structure of the protein. This article will focus on matrix metalloproteinases that are involved in extracellular matrix (ECM) catabolism and serve as important enzymes in many aspects of biology, ranging from cell proliferation, differentiation, and proliferation to cancer, tumor metastasis, inflammation, and other pathologic states. Despite their key role in many normal and pathologic processes, the molecular mechanisms by which zinc‐dependent proteases hydrolyze their physiologic substrates are only known partly. Recent theoretical analyses have suggested reaction models for which limited and controversial experimental evidence exists. Here we will discuss the importance of quantifying the biophysical properties and the structural dynamic behavior of these enzymes to reveal their underlying molecular mechanisms. Such molecular knowledge holds promise in providing the basis for the novel design of specific antagonists as drug candidates for these important enzymes. In addition, we will discuss the use of real‐time spectroscopic tools for studying the reactive metal sites in these enzymes.