Sandbox Reserved 1125: Difference between revisions

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=== Hemopexin domain ===

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 or reduction and alkylation destroys collagenolytic activity (K. Suzuki and H.Nagase, unpublished results).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. When this hemopexin-like domain is removed, the protein loses its ability to cleave collagen. However, neutrophil collagenase is still able to cleave other substrate.

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.[http://www.jleukbio.org/content/81/4/870.full]

Unfortunately, no structure of the full MMP8 protein have 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, by the way you can find 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], good pieces of information on conservations among the MMPs family.

~~[http://www.jleukbio.org/content/81/4/870.full]~~

This domain is localized outside of the catalytic domain shown in this page. It is essential for the substrate recognition of MMP-8 and the single catalytic domain of MMP-8 is not able to cleave collagen. When this hemopexin-like domain is removed, the protein loses its ability to cleave collagen. However, neutrophil collagenase is still able to cleave other substrate.

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.

Sandbox Reserved 1125: Difference between revisions

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@@ Line 52: / Line 52: @@
 === Hemopexin domain ===
 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 destroys 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. When this hemopexin-like domain is removed, the protein loses its ability to cleave collagen. However, neutrophil collagenase is still able to cleave other substrate.
+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.[http://www.jleukbio.org/content/81/4/870.full]
+Unfortunately, no structure of the full MMP8 protein have 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, by the way you can find 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], good pieces of information on conservations among the MMPs family.
-[http://www.jleukbio.org/content/81/4/870.full]
-This domain is localized outside of the catalytic domain shown in this page. It is essential for the substrate recognition of MMP-8 and the single catalytic domain of MMP-8 is not able to cleave collagen. When this hemopexin-like domain is removed, the protein loses its ability to cleave collagen. However, neutrophil collagenase is still able to cleave other substrate.
-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.