Metallo proteinases

All the well-characterized proteinases belong to one or other of four families serine, cysteine, aspartic, or metallo proteinases. This classification is based on a functional criterion, namely, the nature of the most prominent functional group in the active site. Members of the same functional family are usually evolutionarily related, but there are exceptions to this rule. We... 

As with UC, the immune activation seen in CD involves the release of many proinflammatory cytokines. Cytokines thought to play major roles in CD are derived from T-helper type 1 cells and include interferon-y, TNF-a, and IL-1, IL-6, and IL-12. TNF-a is a major contributor to the inflammatory process seen in CD. Its physiologic effects include activation of macrophages, procoagulant effects in the vascular endothelium, and increases in production of matrix metallo-proteinases in mucosal cells.9,15 Excessive production of both... 

In addition, HIV-1 infection also induces the secretion of certain metallo-proteinases (MMP-2, MMP-9) that are capable of cleaving the N-terminus of SDF-1 but not that of the P-chemokines, and this decreases SDF-1 affinity for CXCR4 binding (227-229). Proteolytic modification of SDF-1 by a serum factor(s) that is different from CD26 and MMPs, which results in reduced anti-HIV activity, has been described as well (230). How SDF-1 proteolytic... 

Okuma T, Terasaki Y, Kaikita K, et al. C-C chemokine receptor 2 (CCR2) deficiency improves bleomycin-induced pulmonary fibrosis by attenuation of both macrophage infiltration and production of macrophage-derived matrix metallo-proteinases. J Pathol 2004 204(5) 594-604. 

MacLennan, K., Gallagher, M.P. and Knox, D.P. (1997) Stage-specific serine and metallo-proteinase release by adult and larval Trichostrongylus vitrinus. International foumal for Parasitology 27, 1031-1036. 

Based on their sequence homology, disulfide connectivity, and cysteine location within the sequence and chemistry of the reactive site. Pis can be assigned to distinct families, as classified by Laskowski and Kato. Kunitz-type, Bowman—Birk-type, Potato type I and type II, and squash inhibitors are members of these families shown in Table 3. For inhibitors not falling into these classifications more families have been proposed. Pis can also be classified by their target/mode of action. Plants have been found to express Pis that target serine proteinases, cysteine proteinases, aspartic proteinases, and metallo-proteinases. Serine and cysteine protease inhibitors are the best-studied PIs. ... 

Streptomyces metallo proteinase inhibitor (SMPI) S. nigrescens Stable at 100 °C for 5 min 364,365... 

Bigg HE, Rowan AD. The inhibition of metallo-proteinases as a therapeutic target in rheumatoid arthritis and osteoarthritis. Curr Opin Pharmacol 2001 1 314-20. 

Molecular imaging may potentially address not only the pathophysiology of ischemia but also vascular inflammation causing rupture of atherosclerotic plaques before major ischemic events. Initial approaches have used imaging of "indium radiolabeled monocytes [150], upregulated metallo-proteinases [151], and imaging of apoptosis in atherosclerotic lesions [152]. However, none have evolved into clinically useful tests. 

In the course of a study of structure-based design and synthesis of a potent matrix metallo-proteinase-13 inhibitor based on a pyrrolidinone scaffold, the Suzuki coupling reaction of a,/ -unsaturated /-lactam iodide (40) with 4-methoxyphenylboronic acid was carried out to give the corresponding coupling product in 77 % yield (Eq. (76)) [119]. 

Paul R, Lorenzl S, Koedel U, Sporer B, Vogel U, Frosch M, Pfister HW (1998) Matrix metallo-proteinases contribute to the blood-brain barrier disruption during bacterial meningitis. Aim Neurol 44 592-600... 

H. D. Foda, S. Zucker, Matrix metallo-proteinases in cancer invasion, metastasis and angiogenesis. Drug Discovery Today 2001, 6, 478-482. 

Enzy. abbrev. cheym, = chymotrypsin memb. = membrane M-met. = macrophage-metallo MMP = matrix metallo-proteinase pI.S = plasminogen PMN = polymorpho-nucleates try. = trypsin. 

Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E. and Seiki, M. (1994). A matrix metallo-proteinase expressed on the surface of invasive tumor cells. Nature 570, 61-65. 

Fig. 2. Structure and active site of clostridial neurotoxins. The upper panel shows the structure of CNTs, and the segments that show significant homology between the different serotypes are in black (Minton, 1995). The highest homology is shown by a short segment corresponding to the amino acid residues 216-244 in TeTx. This segment contains the zinc-binding motif of metallo-proteinases (zincins) and it is dissimilar to the consensus sequence of the metzincin metallo-proteinase family (Jiang and Bond, 1992)...

Future important discoveries will be the identification of the neuron-specific receptors of CNTs and of the mode of internalization and membrane translocation of the neurotoxins. Another important line of research is aimed at finding specific inhibitors of these metallo-proteinases. Inhibitors which can cross the neuronal plasmalemma into the cytosol would be potential therapeutic agents in the treatment of tetanus and botulism. The modification of BoNTs to prolong their life time inside the NMJs would be an important research goal to improve the treatment of dystonias. The determination of the three-dimensional structure of these neurotoxins will greatly accelerate the research on these fronts. 

Ikeda U, Shimada K (2003) Matrix metallo-proteinases and coronary artery diseases. Clin Cardiol 26 55-59... 

Implant loosening invariably leads to clinical failure for a variety of reasons, which includes peri-prosthetic fracture of the implant or the bone adjacent to the implant. Numerous failure mechanisms limit the long-term success of endo-prosthetic implants including aseptic osteolysis, aseptic loosening, infection and implant instability (Holt et al., 2007). The key molecules of the host response at the protein level are chemokines, cytokines, nitric oxide metabolites and metallo-proteinases (Gallo et al., 2014). Aseptic osteolysis and subsequent implant failure occur because of a chronic inflammatory response to implant-derived wear particles. Despite many advances related to materials selection, and operation tool and techniques, aseptic osteolysis continues to limit implant longevity. 

Rossetto, O., Deloye, R, Poulain, B., Pellizzari, R., Schiavo, G., and Montecucco, C., The metallo-proteinase activity of tetanus and botulinum neurotoxins, J. Physiol (Paris), 89, 43, 1995. 

Nguyen Q, Murphy G, Hughes CE, Mort JS, Roughley PJ. Matrix metallo-proteinases cleave at two distinct sites on human cartilage link protein. Biochem J 1993 295 595-598. 

Y5. Ylisirnio, S., Hoyhtya, M., and Turpeenniemi-Hujanen, T., Serum matrix metallo-proteinases-2, -9, and tissue inhibitors of metalloproteinases-1, -2 in lung cancer— TlMP-1 as a prognostic marker. Anticancer Res. 20, 1311-1316 (2000). 

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