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| {{STRUCTURE_2ow9| PDB=2ow9 | SCENE= }} | | {{STRUCTURE_2ow9| PDB=2ow9 | SCENE= }} |
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| '''Crystal structure analysis of the MMP13 catalytic domain in complex with specific inhibitor'''
| | ===Crystal structure analysis of the MMP13 catalytic domain in complex with specific inhibitor=== |
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| ==Overview==
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| Matrix metalloproteinase-13 (MMP13) is a Zn(2+)-dependent protease that catalyzes the cleavage of type II collagen, the main structural protein in articular cartilage. Excess MMP13 activity causes cartilage degradation in osteoarthritis, making this protease an attractive therapeutic target. However, clinically tested MMP inhibitors have been associated with a painful, joint-stiffening musculoskeletal side effect that may be due to their lack of selectivity. In our efforts to develop a disease-modifying osteoarthritis drug, we have discovered MMP13 inhibitors that differ greatly from previous MMP inhibitors; they do not bind to the catalytic zinc ion, they are noncompetitive with respect to substrate binding, and they show extreme selectivity for inhibiting MMP13. By structure-based drug design, we generated an orally active MMP13 inhibitor that effectively reduces cartilage damage in vivo and does not induce joint fibroplasias in a rat model of musculoskeletal syndrome side effects. Thus, highly selective inhibition of MMP13 in patients may overcome the major safety and efficacy challenges that have limited previously tested non-selective MMP inhibitors. MMP13 inhibitors such as the ones described here will help further define the role of this protease in arthritis and other diseases and may soon lead to drugs that safely halt cartilage damage in patients.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17623656}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17623656 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17623656}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: S1' mmp13 inhibitor]] | | [[Category: S1' mmp13 inhibitor]] |
| [[Category: Specific mmp13 inhibitor]] | | [[Category: Specific mmp13 inhibitor]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 11:47:26 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:18:49 2008'' |
