title: Glycosylation of matrix metalloproteases and tissue inhibitors: present state, challenges and opportunities.
abstract: Matrix metalloproteases (MMPs) are crucial components of a complex and dynamic network of proteases. With a wide range of potential substrates, their production and activity are tightly controlled by a combination of signalling events, zymogen activation, post-translational modifications and extracellular inhibition. Slight imbalances may result in the initiation or progression of specific disease states, such as cancer and pathological inflammation. As glycosylation modifies the structures and functions of glycoproteins and many MMPs contain N- or O-linked oligosaccharides, we examine, compare and evaluate the evidence for whether glycosylation affects MMP catalytic activity and other functions. It is interesting that the catalytic sites of MMPs do not contain O-linked glycans, but instead possess a conserved N-linked glycosylation site. Both N- and O-linked oligosaccharides, attached to specific protein domains, endow these domains with novel functions such as the binding to lectins, cell-surface receptors and tissue inhibitors of metalloproteases (TIMPs). Validated glycobiological data on N- and O-linked oligosaccharides of gelatinase B/MMP-9 and on O-linked structures of membrane-type 1 MMP/MMP-14 indicate that in-depth research of other MMPs may yield important insights, e.g. about subcellular localizations and functions within macromolecular complexes.
authors.affiliation: KU Leuven-University of Leuven, Rega Institute for Medical Research, Department of Microbiology and Immunology, Laboratory of Immunobiology, B-3000 Leuven, Belgium.
authors.forename: Lise
authors.initials: L
authors.lastname: Boon
authors.affiliation: KU Leuven-University of Leuven, Rega Institute for Medical Research, Department of Microbiology and Immunology, Laboratory of Immunobiology, B-3000 Leuven, Belgium.
authors.forename: Estefania
authors.initials: E
authors.lastname: Ugarte-Berzal
authors.affiliation: KU Leuven-University of Leuven, Rega Institute for Medical Research, Department of Microbiology and Immunology, Laboratory of Immunobiology, B-3000 Leuven, Belgium.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vandooren
authors.affiliation: KU Leuven-University of Leuven, Rega Institute for Medical Research, Department of Microbiology and Immunology, Laboratory of Immunobiology, B-3000 Leuven, Belgium The Glycobiology Institute and Exeter College, University of Oxford, Oxford, UK ghislain.opdenakker@rega.kuleuven.be.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000818:Animals; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding
chemical_list: D037102:Lectins; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases
keywords: MMPs; TIMPs; glycosylation