Sandbox Reserved 1125: Difference between revisions
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The hemopexin domain has two conserved cysteines that are disulfide bonded. Mutation of those cysteines to alanines <ref>PMID:8464863</ref> or reduction and alkylation destroy collagenolytic activity (K. Suzuki and H.Nagase, unpublished results).<ref name="Pdf"/> | The hemopexin domain has two conserved cysteines that are disulfide bonded. Mutation of those cysteines to alanines <ref>PMID:8464863</ref> or reduction and alkylation destroy collagenolytic activity (K. Suzuki and H.Nagase, unpublished results).<ref name="Pdf"/> | ||
It is essential for the substrate recognition of MMP-8 and the single catalytic domain of MMP-8 is not able to cleave collagen. However, neutrophil collagenase is still able to cleave other substrates. | It is essential for the substrate recognition of MMP-8 and the single catalytic domain of MMP-8 is not able to cleave collagen. However, neutrophil collagenase is still able to cleave other substrates. | ||
It seems that the collagen binds to two sites on MMP-8 : one in the catalytic site and another in the hemopexin domain. One hypothesis is that when the collagen binds to both sites, its helical structure is destabilized and unwound. Thus, the cleavage site of collagen is accessible and the cleavage reaction can occur. | It seems that the collagen binds to two sites on MMP-8 : one in the catalytic site and another in the hemopexin domain. One hypothesis is that when the collagen binds to both sites, its helical structure is destabilized and unwound. Thus, the cleavage site of collagen is accessible and the cleavage reaction can occur.<ref>PMID:17185359</ref> | ||
Unfortunately, no structure of the full MMP-8 protein has been crystallized yet, but <scene name='71/719866/Human_prommp-1_structure/1'>here</scene> you can see in orange the hemopexin domain of human pro-MMP1 which is very well conserved between these two proteins. In this article [http://www.fasebj.org/content/12/12/1075.full#ref-27 Matrix metalloproteinases: structures, evolution, and diversification,Irina Massova, Lakshmi P. Kotra, Rafael Fridman and Shahriar Mobashery], there are good pieces of information on conservations among the MMPs family. | Unfortunately, no structure of the full MMP-8 protein has been crystallized yet, but <scene name='71/719866/Human_prommp-1_structure/1'>here</scene> you can see in orange the hemopexin domain of human pro-MMP1 which is very well conserved between these two proteins. In this article [http://www.fasebj.org/content/12/12/1075.full#ref-27 Matrix metalloproteinases: structures, evolution, and diversification,Irina Massova, Lakshmi P. Kotra, Rafael Fridman and Shahriar Mobashery], there are good pieces of information on conservations among the MMPs family. | ||
