Sandbox Reserved 1125: Difference between revisions

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=== Catalytic domain ===

Thanks to X-ray crystallography, the catalytic domain structure has been solved with 1,7 Å resolution (2OY4).This domain is composed of 157 residues, from Met86 to Gly242, organized in <scene name='71/719866/Helixes/4'>three alpha helixes</scene> and <scene name='71/719866/Sheets/3'>five beta sheets</scene>.The protein folding and especially the zinc environment of the collagenase catalytic domain is very close to the astacins and the snake venom metalloproteinases. The catalytic domain alone has proteolytic activity against other protein substrates and synthetic substrates.<ref>PMID:8137810</ref>

Thanks to X-ray crystallography, the catalytic domain structure has been solved with 1,7 Å resolution (2OY4).This domain is composed of 157 residues, from Met86 to Gly242, organized in <scene name='71/719866/Helixes/4'>three alpha helixes</scene> and <scene name='71/719866/Sheets/3'>five beta sheets</scene>.The protein folding and especially the zinc environment of the collagenase catalytic domain is very close to the astacins and the snake venom metalloproteinases. The catalytic domain alone has proteolytic activity against other protein substrates and synthetic substrates.<ref name="X-ray">PMID:8137810</ref>

==== Ca2+ interactions ====

[[Image:CA_pocket_interaction.gif | thumb|CA996 pocket interaction]]This enzyme binds 3 Ca ions, 2 of them in the catalytic domain, which are packed against the top of the beta sheet and mostly have a structural function, stabilizing the catalytic domain.

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The zinc-binding motif HEXGHXXGXXH presents in the catalytic domain is characteristic for the protease activity of MMP-8.

===== Zn999 : the catalytic zinc =====

It is involved in the catalytic activity and is situated at the bottom of the active-site. This ion is penta-coordinated with: His197, His201 and His207 of MMP-8 and with the carbonyl and the hydroxyl oxygen of the hydroxamic acid moiety of the inhibitor. This discovery has been made thanks to the Pro-Leu-Gly-hydroxylamine inhibitor.<ref~~>PMID:8137810</ref~~> On this <scene name='71/719866/Zn999_interactions/5'>link</scene> you can only see the 3 His of MMP-8 with the Zn999. The fourth ligand of the catalytic zinc is a water molecule.

It is involved in the catalytic activity and is situated at the bottom of the active-site. This ion is penta-coordinated with: His197, His201 and His207 of MMP-8 and with the carbonyl and the hydroxyl oxygen of the hydroxamic acid moiety of the inhibitor. This discovery has been made thanks to the Pro-Leu-Gly-hydroxylamine inhibitor.<ref name="X-ay"> On this <scene name='71/719866/Zn999_interactions/5'>link</scene> you can only see the 3 His of MMP-8 with the Zn999. The fourth ligand of the catalytic zinc is a water molecule.

[[Image:ZN pocket interaction.gif | thumb|ZN998 pocket interaction]]

===== Zn998 : the structural zinc =====

The residues involved in the Zn998 interactions are <scene name='71/719866/Zn998/2'>an Asp residue (149) next to three His residues (147, 162 and 175)</scene>. The glutamic acid adjacent to the first histidine is essential for catalysis. It should be noted that scientists were unable to exchange or remove this Zinc in their crystals, which is suggesting that there is a tight interaction with MMP-8.<ref~~>PMID:8137810</ref~~>

The residues involved in the Zn998 interactions are <scene name='71/719866/Zn998/2'>an Asp residue (149) next to three His residues (147, 162 and 175)</scene>. The glutamic acid adjacent to the first histidine is essential for catalysis. It should be noted that scientists were unable to exchange or remove this Zinc in their crystals, which is suggesting that there is a tight interaction with MMP-8.<ref name="X-ray">

=== Hinge domain ===

Sandbox Reserved 1125: Difference between revisions

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@@ Line 34: / Line 34: @@
 === Catalytic domain ===
-Thanks to X-ray crystallography, the catalytic domain structure has been solved with 1,7 Å resolution (2OY4).This domain is composed of 157 residues, from Met86 to Gly242, organized in <scene name='71/719866/Helixes/4'>three alpha helixes</scene> and <scene name='71/719866/Sheets/3'>five beta sheets</scene>.The protein folding and especially the zinc environment of the collagenase catalytic domain is very close to the astacins and the snake venom metalloproteinases. The catalytic domain alone has proteolytic activity against other protein substrates and synthetic substrates.<ref>PMID:8137810</ref>
+Thanks to X-ray crystallography, the catalytic domain structure has been solved with 1,7 Å resolution (2OY4).This domain is composed of 157 residues, from Met86 to Gly242, organized in <scene name='71/719866/Helixes/4'>three alpha helixes</scene> and <scene name='71/719866/Sheets/3'>five beta sheets</scene>.The protein folding and especially the zinc environment of the collagenase catalytic domain is very close to the astacins and the snake venom metalloproteinases. The catalytic domain alone has proteolytic activity against other protein substrates and synthetic substrates.<ref name="X-ray">PMID:8137810</ref>
 ==== Ca2+ interactions ====
 [[Image:CA_pocket_interaction.gif | thumb|CA996 pocket interaction]]This enzyme binds 3 Ca ions, 2 of them in the catalytic domain, which are packed against the top of the beta sheet and mostly have a structural function, stabilizing the catalytic domain.
@@ Line 42: / Line 42: @@
 The zinc-binding motif HEXGHXXGXXH presents in the catalytic domain is characteristic for the protease activity of MMP-8.
 ===== Zn999 : the catalytic zinc =====
-It is involved in the catalytic activity and is situated at the bottom of the active-site. This ion is penta-coordinated with: His197, His201 and His207 of MMP-8 and with the carbonyl and the hydroxyl oxygen of the hydroxamic acid moiety of the inhibitor. This discovery has been made thanks to the Pro-Leu-Gly-hydroxylamine inhibitor.<ref>PMID:8137810</ref> On this <scene name='71/719866/Zn999_interactions/5'>link</scene> you can only see the 3 His of MMP-8 with the Zn999. The fourth ligand of the catalytic zinc is a water molecule.
+It is involved in the catalytic activity and is situated at the bottom of the active-site. This ion is penta-coordinated with: His197, His201 and His207 of MMP-8 and with the carbonyl and the hydroxyl oxygen of the hydroxamic acid moiety of the inhibitor. This discovery has been made thanks to the Pro-Leu-Gly-hydroxylamine inhibitor.<ref name="X-ay"> On this <scene name='71/719866/Zn999_interactions/5'>link</scene> you can only see the 3 His of MMP-8 with the Zn999. The fourth ligand of the catalytic zinc is a water molecule.
 [[Image:ZN pocket interaction.gif | thumb|ZN998 pocket interaction]]
 ===== Zn998 : the structural zinc =====
-The residues involved in the Zn998 interactions are <scene name='71/719866/Zn998/2'>an Asp residue (149) next to three His residues (147, 162 and 175)</scene>. The glutamic acid adjacent to the first histidine is essential for catalysis. It should be noted that scientists were unable to exchange or remove this Zinc in their crystals, which is suggesting that there is a tight interaction with MMP-8.<ref>PMID:8137810</ref>
+The residues involved in the Zn998 interactions are <scene name='71/719866/Zn998/2'>an Asp residue (149) next to three His residues (147, 162 and 175)</scene>. The glutamic acid adjacent to the first histidine is essential for catalysis. It should be noted that scientists were unable to exchange or remove this Zinc in their crystals, which is suggesting that there is a tight interaction with MMP-8.<ref name="X-ray">
 === Hinge domain ===