P53R2: Difference between revisions
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{{STRUCTURE_3hf1| PDB=3hf1 | SIZE=400| SCENE=P53R2/P53r2/3 |right|CAPTION=p53R2 complex with Fe and sulfate ions, [[3hf1]] }} | |||
[[Image:3hf1.png|left|200px]] | |||
[[p53R2]] is an oxydoreductase composed of 351 residues, that could be a new target for an anticancer therapy. It is a small subunit of the ribonucleotide reductase (RNR). | |||
RNR catalyses the reduction of the four nucleotides to desoxyribonucleotides. It exists three classes of RNR. Class I RNR is a tetramer composed of the two types of subunits with stoichiometry α2β2 and three subunits have been identified in mammals : | RNR catalyses the reduction of the four nucleotides to desoxyribonucleotides. It exists three classes of RNR. Class I RNR is a tetramer composed of the two types of subunits with stoichiometry α2β2 and three subunits have been identified in mammals : | ||
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<scene name='Sandbox156/Iron-binding_site/2'>An iron-binding site</scene> is highlighted. But concerning this site, the two monomers are not the same. Actually, the B monomer has two iron-binding site (called Fe2 and Fe1) whereas the A monomer has only one which is Fe2. This can be explained by structural changes in the helix that compose the two monomers. The 37 to 42 N-terminal residues (called the swivel loop) from one monomer can rotate between two conformations and can influence the position of the helix B or D on the opposite monomer. | <scene name='Sandbox156/Iron-binding_site/2'>An iron-binding site</scene> is highlighted. But concerning this site, the two monomers are not the same. Actually, the B monomer has two iron-binding site (called Fe2 and Fe1) whereas the A monomer has only one which is Fe2. This can be explained by structural changes in the helix that compose the two monomers. The 37 to 42 N-terminal residues (called the swivel loop) from one monomer can rotate between two conformations and can influence the position of the helix B or D on the opposite monomer. | ||
[[Image:Thetwomonomers.jpg| thumb | 400px | Figure 1: The structure of the p53R2 protein is shown. P53R2 is built up by two monomers A and B, which contain several iron-binding sites.]] | [[Image:Thetwomonomers.jpg| thumb | center | 400px | Figure 1: The structure of the p53R2 protein is shown. P53R2 is built up by two monomers A and B, which contain several iron-binding sites.]] | ||
The N-terminal residues of the monomer A can stabilize the B helix of the monomer B due to different interactions. R41 of the monomer A forms a salt bridge with E119 of monomer A. This interaction permits the formation of a H-bond between R40 of monomer A with G101of monomer B. Furthermore K37 in monomer A forms a salt bridge with E105 of monomer B and this stabilize its B helix. All the interactions allow D100 of monomer B to be well oriented to bind Fe1 (see Figure 2, Smith P. et al., <ref>PMID:19728742</ref>). | The N-terminal residues of the monomer A can stabilize the B helix of the monomer B due to different interactions. R41 of the monomer A forms a salt bridge with E119 of monomer A. This interaction permits the formation of a H-bond between R40 of monomer A with G101of monomer B. Furthermore K37 in monomer A forms a salt bridge with E105 of monomer B and this stabilize its B helix. All the interactions allow D100 of monomer B to be well oriented to bind Fe1 (see Figure 2, Smith P. et al., <ref>PMID:19728742</ref>). | ||
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p53R2 is included in the RR class I which are characterized by a tyrosyl radical coupled with diiron cluster. A protein which possess tyrosyl radicals with binuclear center is known to have an oxidative or a reductive effect. So for the researchers Lijun Xue et al. <ref>PMID:16488986</ref> it raises the question of the redox properties of p53R2. They found that p53R2 is an antioxidant which can scavenge H2O2. The mitochondrial membrane is sensible to oxidative damage. H2O2 is a reactive oxygen specie (ROS) which can act on cellular growth and survival and is involved in pathogenesis like cancer. p53R2 prevents the loss of mitochondrial membrane by scavenging H2O2. This process protects cells by maintaining their genomic integrity and prevent from cancer. | p53R2 is included in the RR class I which are characterized by a tyrosyl radical coupled with diiron cluster. A protein which possess tyrosyl radicals with binuclear center is known to have an oxidative or a reductive effect. So for the researchers Lijun Xue et al. <ref>PMID:16488986</ref> it raises the question of the redox properties of p53R2. They found that p53R2 is an antioxidant which can scavenge H2O2. The mitochondrial membrane is sensible to oxidative damage. H2O2 is a reactive oxygen specie (ROS) which can act on cellular growth and survival and is involved in pathogenesis like cancer. p53R2 prevents the loss of mitochondrial membrane by scavenging H2O2. This process protects cells by maintaining their genomic integrity and prevent from cancer. | ||
==3D structures of ribonucleotide reductase== | |||
[[Ribonucleotide reductase]] | |||
==References== | |||
<references/> | |||