Title: Structural Bases for Substrate and Inhibitor Recognition by Matrix Metalloproteinases
VOLUME: 15 ISSUE: 22
Author(s):Loretta Aureli, Magda Gioia, Ilaria Cerbara, Susanna Monaco, Giovanni Francesco Fasciglione, Stefano Marini, Paolo Ascenzi, Alessandra Topai and Massimo Coletta
Affiliation:Colosseum Combinatorial Chemistry Centre for Technology (C4T S.C.a r.l.), Via della Ricerca Scientifica s.n.c, I-00133 Roma, Italy.
Keywords:Matrix metalloproteinases, Enzyme-substrate recognition, Enzyme-inhibitor recognition, Structural bases
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.
