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Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said Digimate M-3616 Modem. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention. Description This application claims benefit to provisional application U. The entire teachings of the referenced applications are incorporated herein by reference. The metalloproteinases may be one of the older classes of proteases and are found in bacteria, fungi as well as in higher organisms.

They differ widely in their sequences and their structures, but many contain a zinc ion. In some cases, zinc may be replaced by another metal such as cobalt or nickel.

Such metal ion coordination facilitates Digimate M-3616 Modem through the stabilization of a noncovalent, tetrahedral intermediate after the attack of a metal-bound water molecule on the carbonyl group of the scissile bond. This intermediate Digimate M-3616 Modem further decomposed by transfer of the glutamic acid proton to the leaving group. Metal ion coordination is thought to stabilize the negative charges formed within the active site of the enzyme during catalysis.

Such stabilization lowers the transition state energy requirements, and thus results in significant rate enhancements during enzymatic catalysis over non-metal ion coordination conditions Fersht, A. Freeman and Company, New York, The prototype of this family is a secreted O-sialoglycoprotein endopeptidase so called because it has specificity Digimate M-3616 Modem cleavage of proteins which contain O-sialoglycans attached to serine and threonine residues from the Digimate M-3616 Modem [] pasteurella haemolytica Abdullah et al. Substrate proteins for the P.

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Digimate M-3616 Modem Although the [] P. In addition similar sequences have been identified from mycoplasma genitalium, mycoplasma pneumoniae, archaeoglobus fulgidus, pyrococcus horikoshii, chlamydia trachomatis, streptomyces coelicolor, mycobacterium tuberculosis, mycobacterium leprae and bacillus subtilis. The MP-1 gene of the present invention represents the first described mammalian homologue belonging to the m22 class of metalloproteinases.

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Metalloproteinases Digimate M-3616 Modem Disease [] Limited-proteolysis by metalloproteases plays a central regulatory role in many physiological and pathophysiological processes. There are many examples of inhibitors of metalloproteases that are useful medications in the treatment of hypertension, heart failure, various forms of cancer and other diseases. There is a balance between the synthesis and degradation of extracellular matrix proteins in the process Digimate M-3616 Modem synapse formation during development and regeneration.

The timing of MP activation is therefore potentially critical. Some MPs have been shown to be upregulated in the spinal cord either during development or in pathological states such as multiple sclerosis, experimental autoimmune encephalomyelitis, and amyotrophic lateral sclerosis. Since MPs degrade extracellular matrix Digimate M-3616 Modem, they would be toxic to developing neurons that depend upon the matrix proteins for survival, neurite outgrowth, and synapse formation. Degradation of the matrix proteins would Digimate M-3616 Modem cause the breakdown of the blood brain barrier and infiltration of immune cells into the CNS, which occurs in inflammatory conditions such as MS. All of which might be therapeutically useful under different circumstances.

The metalloproteinase of the present invention can also be Digimate M-3616 Modem as a scaffold to tailor-make specific metalloproteinase inhibitors. In addition, there are several significant amino acid differences. First, an analysis was performed to evaluate the polynucleotide and polypeptide sequence of MP-1 of the present invention to its corresponding genomic sequence Genbank Accession No.


In addition, the 25 amino acid insertion observed in gi was considered an intron by the GenewiseDB program. When gi was analyzed against AC using GenewiseDB, the presence of the 25 amino acid insertion caused a frameshift in the coding sequence. Thus, the 25 Digimate M-3616 Modem acid insertion present in gi represents an unspliced intron in the cDNA sequence. Thus, Digimate M-3616 Modem upon the indicia provided above, the MP-1 polypeptide, in addition to, its encoding polynucleotide are believed to represent the physiologically active form of the enzyme. Also provided are polypeptide alignments illustrating the strong conservation of the MP-1 polypeptide to other known metalloproteinases.


Data is also provided illustrating the unique tissue expression profile of the MP-1 polypeptide in spinal cord tissues, which has not been appreciated heretofore. Synthetic methods for producing the polypeptides and polynucleotides of the present invention are Digimate M-3616 Modem. The invention further relates to screening methods for identifying binding partners of the polypeptides.

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The present invention also Digimate M-3616 Modem to recombinant vectors, which include the isolated nucleic acid molecules of Digimate M-3616 Modem present invention, and to host cells containing the recombinant vectors, as well as to methods of making such vectors and host cells, in addition to their use in the production of MP-1 polypeptides or peptides using recombinant techniques. Such storage medium encoded with these data are capable of displaying on a computer screen or similar viewing device, a three-dimensional graphical representation of a molecule or molecular complex which comprises said regions or similarly shaped homologous regions. The methods include three dimensional model building homology modeling and methods of computer assisted-drug design which can be used to identify compounds which bind or modulate the forementioned regions of the MP-1 polypeptide.

Such compounds are potential inhibitors of MP-1 or its homologues.

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A machine-readable data storage medium, comprising a data storage material encoded with machine readable data, wherein the data is defined by the set of structure coordinates of the model MP-1 according to Table III, or a homologue of said Digimate M-3616 Modem, wherein said homologue comprises backbone atoms that have a root mean square deviation from the backbone atoms of not more than about 4. The standard one-letter abbreviation for amino acids is used to illustrate the deduced amino acid sequence. An analysis of the MP-1 polypeptide determined that it comprised the following features: The predicted metal binding domain amino acids are believed to coordinate a zinc ion within the active site domain of the MP-1 polypeptide and facilitate catalysis of appropriate metalloproteinase substrates.

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