Structural Bases for Substrate and Inhibitor Recognition by Matrix Metalloproteinases

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.,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.

Cite this article as:

Aureli Loretta, Gioia Magda, Cerbara Ilaria, Monaco Susanna, Fasciglione Francesco Giovanni, Marini Stefano, Ascenzi Paolo, Topai Alessandra and Coletta Massimo, Structural Bases for Substrate and Inhibitor Recognition by Matrix Metalloproteinases, Current Medicinal Chemistry 2008; 15(22) . https://dx.doi.org/10.2174/092986708785747490