Sandbox Reserved 1125: Difference between revisions
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=== Catalytic domain === | === 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 name="X-ray">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 ==== | ==== 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 have mostly a structural function, stabilizing the catalytic domain.<ref name="X-ray"/> | [[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 have mostly a structural function, stabilizing the catalytic domain.<ref name="X-ray"/> | ||
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===== Zn998 : the structural zinc ===== | ===== 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 name="X-ray"/> | 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"/> | ||
==== Subsites ==== | |||
Besides the catalytic site, the MMPs have other sites called subsites which can also interact with the substrates and inhibitors. Conventionally, the subsites on the left of the catalytic Zn2+ are designated as S1, S2, S3,..., Sn and the ones on the right are known as S1', S2', etc. | |||
One of these subsites, the S1' pocket, is the main subsite for the substrate recognition. Thus, this pocket is variable in amino acid composition and depth and can be used to classify the MMPs. | |||
MMP-8 belongs to the class of the intermediate MMPs according to the depth of its <scene name='71/719866/S1prime_pocket/1'>S1' pocket</scene>.<ref>PMID:22642189</ref> | |||
This pocket is delimited by the Leu193, Val194, His197, Leu214, Tyr216, Tyr219, Ala220 and Arg222 residues.<ref>PMID:17275314</ref>. | |||
Moreover this pocket is rich in hydrophobic amino acids, what is suitable for binding to the substrate of MMP-8. | |||
=== Hinge domain === | === Hinge domain === | ||
