P53R2: Difference between revisions
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On the contrary R40 of monomer B is bound to E119 of the same monomer and so it can not bind to G101 of the monomer A and the consequence is that F42 disturb the B helix of monomer A. D100 can not interact with Fe1. This explain why the monomer A has only one iron-binding site whereas the monomer B has two (see Figure 2, Smith P. et al., 2009, 2.6 A ° X-ray Crystal Structure of Human p53R2, a p53-Inducible Ribonucleotide Reductase). | On the contrary R40 of monomer B is bound to E119 of the same monomer and so it can not bind to G101 of the monomer A and the consequence is that F42 disturb the B helix of monomer A. D100 can not interact with Fe1. This explain why the monomer A has only one iron-binding site whereas the monomer B has two (see Figure 2, Smith P. et al., 2009, 2.6 A ° X-ray Crystal Structure of Human p53R2, a p53-Inducible Ribonucleotide Reductase). | ||
[[Image:Figure 2.jpg]] | |||
Compare to the M2 subunit, these iron-binding sites are less efficient. This is due to the different conformations that the p53R2 subunit can adopt (stabilization or not of the two helix B and D). | Compare to the M2 subunit, these iron-binding sites are less efficient. This is due to the different conformations that the p53R2 subunit can adopt (stabilization or not of the two helix B and D). | ||
Furthermore the iron is the cofactor of the reaction catalyses by the RNR. The fact that in the p53R2 subunit the iron-binding is less efficient permits to imagine a specific anti-cancer therapy that targets these region, for example the drug [http://en.wikipedia.org/wiki/Deferoxamine deferoxamine mesylate] an iron chelator. Without iron, the reduction of the nucleotides can not take place and this could avoid the proliferation of cancer cells. | Furthermore the iron is the cofactor of the reaction catalyses by the RNR. The fact that in the p53R2 subunit the iron-binding is less efficient permits to imagine a specific anti-cancer therapy that targets these region, for example the drug [http://en.wikipedia.org/wiki/Deferoxamine deferoxamine mesylate] an iron chelator. Without iron, the reduction of the nucleotides can not take place and this could avoid the proliferation of cancer cells. | ||
