1gxd: Difference between revisions
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==Overview== | ==Overview== | ||
Matrix metalloproteinases (MMPs) are a family of multidomain enzymes, involved in the physiological degradation of connective tissue, as well as, in pathological states such as tumor invasion and arthritis. Apart from, transcriptional regulation, MMPs are controlled by proenzyme activation, and a class of specific tissue inhibitors of metalloproteinases (TIMPs), that bind to the catalytic site. TIMP-2 is a potent inhibitor of MMPs, but, it has also been implicated in a unique cell surface activation mechanism, of latent MMP-2/gelatinase A/type IV collagenase (proMMP-2), through its, binding to the hemopexin domain of proMMP-2 on the one hand and to a, membrane-type MMP activator on the other. The present crystal structure of, the human proMMP-2/TIMP-2 complex reveals an interaction between the, hemopexin domain of proMMP-2 and the C-terminal domain of TIMP-2, leaving, the catalytic site of MMP-2 and the inhibitory site of TIMP-2 distant and, spatially isolated. The interfacial contact of these two proteins is, characterized by two distinct binding regions composed of alternating, hydrophobic and hydrophilic interactions. This unique structure provides, information for how specificity for noninhibitory MMP/TIMP complex, formation is achieved. | Matrix metalloproteinases (MMPs) are a family of multidomain enzymes, involved in the physiological degradation of connective tissue, as well as, in pathological states such as tumor invasion and arthritis. Apart from, transcriptional regulation, MMPs are controlled by proenzyme activation, and a class of specific tissue inhibitors of metalloproteinases (TIMPs), that bind to the catalytic site. TIMP-2 is a potent inhibitor of MMPs, but, it has also been implicated in a unique cell surface activation mechanism, of latent MMP-2/gelatinase A/type IV collagenase (proMMP-2), through its, binding to the hemopexin domain of proMMP-2 on the one hand and to a, membrane-type MMP activator on the other. The present crystal structure of, the human proMMP-2/TIMP-2 complex reveals an interaction between the, hemopexin domain of proMMP-2 and the C-terminal domain of TIMP-2, leaving, the catalytic site of MMP-2 and the inhibitory site of TIMP-2 distant and, spatially isolated. The interfacial contact of these two proteins is, characterized by two distinct binding regions composed of alternating, hydrophobic and hydrophilic interactions. This unique structure provides, information for how specificity for noninhibitory MMP/TIMP complex, formation is achieved. | ||
==Disease== | |||
Known diseases associated with this structure: Osteolysis, idiopathic, Saudi type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120360 120360]], Winchester syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120360 120360]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:09:56 2007'' | ||
