Metalloproteinase

Design and therapeutic application of matrix metalloproteinase heterocyclic inhibitors 99CRV2735. 

Marimastat Metalloproteinase inhibitor, inhibits endothelial cell invasion... 

Vascular Indothelial Growth Factor Matrix Metalloproteinases... 

MM P-9 Matric metalloproteinase Decrease of in vivo metastatic ability... 

Enzyme inhibitors (e.g. metalloproteinases, cathepsin K) Purinergic modulators... 

ECEs are metalloproteinases that are homologous to the neutral endopeptidase (NEP, E-24.11, neprilysin) unlike NEP, however, they form disulfide-bonded homodimers. In man, with ECE-1 and ECE-2, two isoforms are known, which are encoded by two separate genes. For ECE-1 four different variants have been identified (ECE-1 a-d), which are generated by the use of alternative promoters (Table 2). The ECE-1 isoforms only differ in their N-terminal amino acid sequence. For ECE-2, a single gene product has been described in... 

Activation of matrix metalloproteinases (MMP) is also involved in vascular and cardiac remodelling. For example, the fibrillar collagen matrix of the heart... 

Matrix Metalloproteinases Tumor Necrosis Factor Apoptosis... 

The enzymatic activity of these potentially harmful enzymes is tightly controlled. Once transcribed into protein, MMPs are expressed as inactive zymogens and require distinct activation processes to convert them into active enzymes. After secretion, MMP-activity is regulated by the noncovalent binding of tissue inhibitors of metalloproteinases ( TIMPs) as shown in Fig. 2 for MMP-2 and TIMP-2. Four TIMPs have been identified so far TIMP-1, TIMP-2, TIMP-3, and TIMP-4. All known MMPs can be inhibited by at least one of the four known TIMPs. Nevertheless, individual differences with regard to bond strength and thus the magnitude of inhibition of a particular MMP do exist. 

Matrix Metalloproteinases. Table 1 MMPs and their genes known so far... 

Matrix Metalloproteinases. Figure 1 Domain organization of different mammalian MMPs. 

Matrix Metalloproteinases. Figure 2 ProMMP-2-TIMP-2 structure (adopted from [4]). TIMP-2 cartoon and transparent surface structure is shown in blue, MMP-2 in red. The C-terminal ends of both molecules are marked as spheres. 

Somerville RP, Oblander SA, Apte SS (2003) Matrix metalloproteinases old dogs with new tricks. Genome Biol 4 216... 

Stetler-Stevenson WG (1999) Matrix metalloproteinases in angiogenesis a moving target for therapeutic intervention. J Clin Invest 103 1237-1241... 

Morgunova E, Tuuttila A, Bergmann U et al (2002) Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2. Proc Natl Acad Sci USA 99 7414—7419... 

Metalloproteinases are a subgroup of proteinases. They are responsible for the cleavage of peptide bonds within a protein (proteolysis). Metalloproteinases contain a metal ion in the active center and are divided into four subclasses dependent on their mechanism of catalysis. 

The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitor of metalloproteinases (TIMPs), which comprise a family of four protease inhibitors TIMP-1, TIMP-2, TIMP-3, and TIMP-4. Overall, all MMPs are inhibited by TIMPs once they are activated but the gelatinases (MMP-2 and MMP-9) can form complexes with TIMPs when the enzymes are in the latent form. 

Prenzel N, Zwick E, Daub H et al (1999) EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 402 884-888... 

Matrix Metalloproteinases Matrix-assisted Laser Desorption/Ionization Mass Spectrometry... 

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