Structural Bases for Substrate and Inhibitor Recognition by Matrix Metalloproteinases

Loretta      Aureli; Magda      Gioia; Ilaria      Cerbara; Susanna      Monaco; Giovanni   Francesco   Fasciglione; Stefano      Marini; Paolo      Ascenzi; Alessandra      Topai; Massimo      Coletta

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases which are involved in the proteolytic processing of several components of the extracellular matrix. As a consequence, MMPs are implicated in several physiological and pathological processes, like skeletal growth and remodelling, wound healing, cancer, arthritis, and multiple sclerosis, raising a very widespread interest toward this class of enzymes as potential therapeutic targets. Here, structure-function relationships are discussed to highlight the role of different MMP domains on substrate/inhibitor recognition and processing and to attempt the formulation of advanced guidelines, based on natural substrates, for the design of inhibitors more efficient in vivo.

Keywords: Matrix metalloproteinases, Enzyme-substrate recognition, Enzyme-inhibitor recognition, Structural bases