Sandbox Reserved 1508: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 25: | Line 25: | ||
== 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 catalytic site, weakening the O–O bond and stabilizing the transition state between the proximal O. | 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. | ||
At the active site of the enzyme, a pyrodoxal-phosphate cofactor is covalently linked to the Lysine 51, an invariant residue. A parallel β-sheet associated with three α-helices are part of the N terminal domain (residues 46 to 153). Two of those α-helices are part of the dimer interface and the third one is partly forming the entrance of the active site as on the other side of the β-sheet. On the other hand the C-terminal domain is made of 6-stranded mixed β-sheets surrounded by four α-helices (two on each sides) and of residues with a unique insertion of eight amino acids within them. (Ågren et al, 2008) | |||
All those compounds allow the enzyme to have several conformations : an open one, a closed one (when a substrate is bound to the enzyme) and an inhibited form (when there is a chlorite bound at an allosteric site). (Ågren et al, 2008) | |||
Besides, within the catalytic site hydrogen bounds can be made with the phosphate on Arg 220 as this way interactions can also be made with the hydroxyl group of Tyr 152 and the side chain of Thr 185. (Ågren et al, 2008) | |||
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. | ||
