User:Julie Frentzel/Sandbox 1
From Proteopedia
(New page: 2oxu protein) |
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2oxu protein | 2oxu protein | ||
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| + | '''Introduction''' | ||
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| + | 2oxu is a human protease. It belongs to the Matrix Metalloproteinase’s family (MMPs). Theses MMPs are secreted as inactive proproteins and then activated after a cleavage by extracellular proteinases. | ||
| + | MMPs are sorted into 17 classes depending on their localization in the cell, and on their substrates. For instance, 2Oxu is a macrophage metalloelastane indexed in MMP12 subfamily. To make things clear, it allows the migration of the macrophages in tissues by hydrolysing soluble and insoluble elastin of the extracellular matrix. This hydrolysis involves two cofactors: zinc and calcium. Zinc atoms are part of the enzyme whereas Ca2+ atoms are hydrogen bounded to the backbone of the protein. | ||
| + | In healthy cells, 2oxu is implied in tissue remodelling and cell signalling. | ||
| + | Because of its activity, this protein is also involved in metastasis and tumor development; that's why it is considered as an important target for drug therapies. | ||
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| + | ---- | ||
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| + | '''Structure / function relationship''' | ||
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| + | Thanks to X-ray crystallography, the structure of 2oxu has been solved with 1,24 Å resolution. | ||
| + | This enzyme consists of four alpha helix and five beta sheets organized like following. => STRUCTURE DRAWING | ||
| + | |||
| + | The hydrolysis of the Substrate can be divided in four essential events: | ||
| + | |||
| + | 1- Substrate's fixation | ||
| + | |||
| + | 2- Substrate's cleavage | ||
| + | |||
| + | 3- First fragment's release | ||
| + | |||
| + | 4- Second fragment's release | ||
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| + | The experiment was made with a collagen derived substrate to lower the enzymatic activity, so that the mechanism can be studied. | ||
| + | In the detailed experiment implying 2oxu, a collagen derived substrate is the chosen one: Indeed, when elastin is used, its hydrolysis is so fast that no peptide cleavage mechanism can be visualized. | ||
| + | |||
| + | The substrate polypeptide sequence which is recognized by the enzyme is common to both molecules (elastin and collagen): ProGlnGly(206)IleAlaGly(209). It is known to be cleaved between Gly(206) and ILE. | ||
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| + | Before the addition of the substrate, the active site is closed. | ||
| + | |||
| + | |||
| + | 1) Substrate's fixation | ||
| + | |||
| + | The active site of the enzyme is composed by one Glu residue near 3 His residues which maintain a Zn2+ atom. This atom is also coordinated with three water molecules. One of them is as well bound to the Glu residue thanks to a hydrogen bond. The second Zn2+ atom is not involved in the active site. | ||
Revision as of 10:28, 1 November 2009
2oxu protein
Introduction
2oxu is a human protease. It belongs to the Matrix Metalloproteinase’s family (MMPs). Theses MMPs are secreted as inactive proproteins and then activated after a cleavage by extracellular proteinases. MMPs are sorted into 17 classes depending on their localization in the cell, and on their substrates. For instance, 2Oxu is a macrophage metalloelastane indexed in MMP12 subfamily. To make things clear, it allows the migration of the macrophages in tissues by hydrolysing soluble and insoluble elastin of the extracellular matrix. This hydrolysis involves two cofactors: zinc and calcium. Zinc atoms are part of the enzyme whereas Ca2+ atoms are hydrogen bounded to the backbone of the protein. In healthy cells, 2oxu is implied in tissue remodelling and cell signalling. Because of its activity, this protein is also involved in metastasis and tumor development; that's why it is considered as an important target for drug therapies.
Structure / function relationship
Thanks to X-ray crystallography, the structure of 2oxu has been solved with 1,24 Å resolution. This enzyme consists of four alpha helix and five beta sheets organized like following. => STRUCTURE DRAWING
The hydrolysis of the Substrate can be divided in four essential events:
1- Substrate's fixation
2- Substrate's cleavage
3- First fragment's release
4- Second fragment's release
The experiment was made with a collagen derived substrate to lower the enzymatic activity, so that the mechanism can be studied. In the detailed experiment implying 2oxu, a collagen derived substrate is the chosen one: Indeed, when elastin is used, its hydrolysis is so fast that no peptide cleavage mechanism can be visualized.
The substrate polypeptide sequence which is recognized by the enzyme is common to both molecules (elastin and collagen): ProGlnGly(206)IleAlaGly(209). It is known to be cleaved between Gly(206) and ILE.
Before the addition of the substrate, the active site is closed.
1) Substrate's fixation
The active site of the enzyme is composed by one Glu residue near 3 His residues which maintain a Zn2+ atom. This atom is also coordinated with three water molecules. One of them is as well bound to the Glu residue thanks to a hydrogen bond. The second Zn2+ atom is not involved in the active site.
