Matrix metalloproteinases – an overview

Abstract

Matrix metalloproteinases (MMPs, matrixins) are a family of secreted and membrane-bound zinc-dependent endopeptidases that have the combined capacity to degrade all the components of the extracellular matrix. These enzymes have a common zinc-binding motif (HEXXHXXGXXH) in their active site and a conserved methionine turn following the active site. MMP enzymes are strongly involved in a kaleidoscope of normal, pathological, physiological, and biological processes such as embryogenesis, normal tissue remodeling, wound healing, and angiogenesis, and in diseases such as atheroma, arthritis, cancer, and tissue ulceration. MMPs play a significant role in vascular remodeling. Broad-spectrum metalloproteinase inhibitors as potential therapeutics have been developed to explore the involvement of MMPs in various diseases.

Sequential Amyloid-β Degradation by the Matrix Metalloproteases MMP-2 and MMP-9

“…A␤ Peptides-Synthetic homologues of A␤42, A␤40, the C-terminal truncated fragments A␤ , A␤ , and A␤ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), as well as the A␤40 genetic variant containing the L34V substitution were synthesized using N-tert-butyloxycarbonyl chemistry by James I. Elliott at Yale University. For quantitative MS, isotopically labeled peptide standards of A␤42, A␤40, and the C-terminal truncated fragments A␤ , A␤ , and A␤ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) were synthesized with deuterated [ 2 H]phenylalanine residues; labels were introduced at positions 4, 19, and 20 in A␤42, A␤40, A␤34, and A␤30, whereas A␤(1-16) contained a single labeled residue at position 4.…”

“…For quantitative MS, isotopically labeled peptide standards of A␤42, A␤40, and the C-terminal truncated fragments A␤ , A␤ , and A␤ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) were synthesized with deuterated [ 2 H]phenylalanine residues; labels were introduced at positions 4, 19, and 20 in A␤42, A␤40, A␤34, and A␤30, whereas A␤(1-16) contained a single labeled residue at position 4. All synthetic peptides were purified by reverse phase-high performance liquid chromatography, molecular masses corroborated by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MS, and concentrations assessed by amino acid analysis, as described previously (16,18).…”

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

“…During invasion malignant cells detach from primary tumour and invade through basement membrane and stromal ECM (Vihinen and Kahari, 2002). Proteolytic degradation of basement membrane and ECM is an essential step for invasion and requires proteases (Sekhon, 2010). The steps involved in the process of invasion are shown in Figure 3.…”

“…MMPs are important not only in normal, physiological and biological processes such as embryogenesis, normal tissue remodelling, wound healing and angiogenesis but also in diseases such as arthritis, cancer& tissue ulceration (Sekhon, 2010).…”

“…identified among vertebrates, 23 of them have been found in humans Vihinen and Kahari, 2002;Chau dhary et al, 2010;Sekhon, 2010) (Table 1). Several MMPs have been localised to the same chromosomal location 11q23, a region that shows amplification in several solid tumours (Curran and Murray, 1999).…”