Sandbox Reserved 1508
From Proteopedia
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<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
The protein 5C04 is classified as an oxidoreductase. We found it in the ''Mycobacterium tuberculosis'' organism, especially in the strain ATCC 25618/H37Rv. It can be expressed in ''Escherichia Coli'' bacteria. This is a pathogenic protein which is involved in the tuberculosis. Its pathogenicity is due to a specific mutation in the active site of peroxiredoxins. | The protein 5C04 is classified as an oxidoreductase. We found it in the ''Mycobacterium tuberculosis'' organism, especially in the strain ATCC 25618/H37Rv. It can be expressed in ''Escherichia Coli'' bacteria. This is a pathogenic protein which is involved in the tuberculosis. Its pathogenicity is due to a specific mutation in the active site of peroxiredoxins. | ||
| - | <ref>DOI: 10.2210/pdb5C04/pdb/> | + | <ref>DOI: 10.2210/pdb5C04/pdb/<ref> |
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== Background == | == Background == | ||
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According to PDB code 5C04, the structure of the protein has been characterized thanks to crystallography (X-Ray diffraction). The scientists obtained a resolution of 1.45 Å, a R-value free of 0.198 and a R-value work of 0.166. The structure of the 5C04 protein has in total 2 chains (A and B) represented by one sequence-unique entity (one polymer) of L-type polypeptide. Its length is 153 residues. Its secondary structure shows that 27% of alpha helix are composed by six helix for a total of 42 residues; and 27% of beta sheet are composed by 11 strands for also a total of 42 residues. | According to PDB code 5C04, the structure of the protein has been characterized thanks to crystallography (X-Ray diffraction). The scientists obtained a resolution of 1.45 Å, a R-value free of 0.198 and a R-value work of 0.166. The structure of the 5C04 protein has in total 2 chains (A and B) represented by one sequence-unique entity (one polymer) of L-type polypeptide. Its length is 153 residues. Its secondary structure shows that 27% of alpha helix are composed by six helix for a total of 42 residues; and 27% of beta sheet are composed by 11 strands for also a total of 42 residues. | ||
| - | Catalytic site | + | == Catalytic site == |
| - | The article The active site architecture in peroxiredoxins: a case study on ''Mycobacterium tuberculosis'' AhpE (Zeida et al, 2015) describe the active site of the protein 5C04 by using the model ''Mycobacterium tuberculosis'' AhpE (alkyl hydroperoxide reductases E). Researchers noticed that cysteine is not essential for the binding of H2O2 to the active site of peroxiredoxin. There are conserved residues in the active site which are important for H2O2 binding and reduction: the threonine from the PxxxTxxC sequence motif and an arginine distant in a sequence but close to the active site (Zeida et al, 2015). The conserved arginine plays a pivotal role in bringing the oxygen of the peroxide closer to the | + | The article The active site architecture in peroxiredoxins: a case study on ''Mycobacterium tuberculosis'' AhpE (Zeida et al, 2015) describe the active site of the protein 5C04 by using the model ''Mycobacterium tuberculosis'' AhpE (alkyl hydroperoxide reductases E). Researchers noticed that cysteine is not essential for the binding of H2O2 to the active site of peroxiredoxin. There are conserved residues in the active site which are important for H2O2 binding and reduction: the threonine from the PxxxTxxC sequence motif and an arginine distant in a sequence but close to the active site (Zeida et al, 2015). The conserved arginine plays a pivotal role in bringing the oxygen of the peroxide closer to the catalytic site, weakening the O–O bond and stabilizing the transition state between the proximal O. |
The cysteine are polar uncharged amino acids. It has the particularity to be easily oxidized to form a dimer containing disulfide bridge between two cysteine. Important protein nonpolar residues in the dimer interface have been shown. The proximity between this hydrophobic region and Cys residues allows this kind of substrates to lay most of their aliphatic carbon chains over the patch, supporting the direct interaction of the peroxide group with the reactive thiolate group (Zeida et al, 2015). There is a complex hydrogen bound network which is involved in the Thr and oxygen bonding. | The cysteine are polar uncharged amino acids. It has the particularity to be easily oxidized to form a dimer containing disulfide bridge between two cysteine. Important protein nonpolar residues in the dimer interface have been shown. The proximity between this hydrophobic region and Cys residues allows this kind of substrates to lay most of their aliphatic carbon chains over the patch, supporting the direct interaction of the peroxide group with the reactive thiolate group (Zeida et al, 2015). There is a complex hydrogen bound network which is involved in the Thr and oxygen bonding. | ||
| - | Additionally, there is fatty acid, derived from hydroperoxide, involved in the reduction of the H2O2. | + | Additionally, there is fatty acid, derived from hydroperoxide, involved in the reduction of the H2O2. Peroxidase involves a proton transfer from the both oxygens that occurs after transtion state. |
The oxidized reactive cystein have an unprotonated form of sulfenic acid and a protonated form. The reduction mechanism of these subtrate is the same as for H2O2. | The oxidized reactive cystein have an unprotonated form of sulfenic acid and a protonated form. The reduction mechanism of these subtrate is the same as for H2O2. | ||
Revision as of 17:48, 10 January 2019
| This Sandbox is Reserved from 06/12/2018, through 30/06/2019 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1480 through Sandbox Reserved 1543. |
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The protein 5C04
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References
Ågren, Daniel, Robert Schnell, Wulf Oehlmann, Mahavir Singh, et Gunter Schneider. « Cysteine Synthase (CysM) of Mycobacterium Tuberculosis Is an O -Phosphoserine Sulfhydrylase: EVIDENCE FOR AN ALTERNATIVE CYSTEINE BIOSYNTHESIS PATHWAY IN MYCOBACTERIA ». Journal of Biological Chemistry 283, nᵒ 46 (14 novembre 2008): 31567‑74. https://doi.org/10.1074/jbc.M804877200.
Burns, Kristin E., Sabine Baumgart, Pieter C. Dorrestein, Huili Zhai, Fred W. McLafferty, et Tadhg P. Begley. « Reconstitution of a New Cysteine Biosynthetic Pathway in Mycobacterium t Uberculosis ». Journal of the American Chemical Society 127, nᵒ 33 (août 2005): 11602‑3. https://doi.org/10.1021/ja053476x.
Pedre, Brandán, Laura A. H. van Bergen, Anna Palló, Leonardo A. Rosado, Veronica Tamu Dufe, Inge Van Molle, Khadija Wahni, et al. « The Active Site Architecture in Peroxiredoxins: A Case Study on Mycobacterium Tuberculosis AhpE ». Chemical Communications 52, nᵒ 67 (2016): 10293‑96. https://doi.org/10.1039/C6CC02645A.
Rhee, Sue Goo, et Hyun Ae Woo. « Multiple Functions of Peroxiredoxins: Peroxidases, Sensors and Regulators of the Intracellular Messenger H 2 O 2 , and Protein Chaperones ». Antioxidants & Redox Signaling 15, nᵒ 3 (août 2011): 781‑94. https://doi.org/10.1089/ars.2010.3393.
Zeida, Ari, Aníbal M. Reyes, Pablo Lichtig, Martín Hugo, Diego S. Vazquez, Javier Santos, F. Luis González Flecha, Rafael Radi, Dario A. Estrin, et Madia Trujillo. « Molecular Basis of Hydroperoxide Specificity in Peroxiredoxins: The Case of AhpE from Mycobacterium Tuberculosis ». Biochemistry 54, nᵒ 49 (15 décembre 2015): 7237‑47. https://doi.org/10.1021/acs.biochem.5b00758.
