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| '''Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features'''
| | ===Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features=== |
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| ==Overview==
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| Membrane-type matrix metalloproteinases (MT-MMPs) have attracted strong attention, because four of them can activate a key player in the tumor scenario, proMMP-2/progelatinase A. In addition to this indirect effect on the cellular environment, these MT-MMPs degrade extracellular matrix proteins, and their overproduction is associated with tumor growth. We have solved the structure of the catalytic domain (cd) of MT3-MMP/MMP-16 in complex with the hydroxamic acid inhibitor batimastat. CdMT3-MMP exhibits a classical MMP-fold with similarity to MT1-MMP. Nevertheless, it also shows unique properties such as a modified MT-specific loop and a closed S1' specificity pocket, which might help to design specific inhibitors. Some MT-MMP-specific features, derived from the crystal structures of MT-1-MMP determined previously and MT3-MMP, and revealed in recent mutagenesis experiments, explain the impaired interaction of the MT-MMPs with TIMP-1. Docking experiments with proMMP-2 show some exposed loops including the MT-loop of cdMT3-MMP involved in the interaction with the proMMP-2 prodomain in the activation encounter complex. This model might help to understand the experimentally proven importance of the MT-loop for the activation of proMMP-2.
| | The line below this paragraph, {{ABSTRACT_PUBMED_14741217}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 14741217 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_14741217}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Mt3-mmp]] | | [[Category: Mt3-mmp]] |
| [[Category: Protease]] | | [[Category: Protease]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:39:54 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:22:15 2008'' |
