title: Structural bases for substrate and inhibitor recognition by matrix metalloproteinases.
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.
authors.affiliation: Colosseum Combinatorial Chemistry Centre for Technology (C4T S.C.a r.l.), Via della Ricerca Scientifica s.n.c, I-00133 Roma, Italy. loretta.aureli@uniroma2.it
authors.forename: Loretta
authors.initials: L
authors.lastname: Aureli
authors.forename: Magda
authors.initials: M
authors.lastname: Gioia
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cerbara
authors.forename: Susanna
authors.initials: S
authors.lastname: Monaco
authors.forename: Giovanni Francesco
authors.initials: GF
authors.lastname: Fasciglione
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Topai
authors.forename: Massimo
authors.initials: M
authors.lastname: Coletta
mesh_terms: D000818:Animals; D019295:Computational Biology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases