Ribonucleotide reductase: Difference between revisions

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Michal Harel, Jaime Prilusky, Alexander Berchansky, Joel L. Sussman

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-{{STRUCTURE_2xo4|  PDB=2xo4  | SIZE=400| SCENE= |right|CAPTION=Ribonucleotide from ''E. coli''  large subunit and small subunit peptide, [[2xo4]] }}
+<StructureSection load='' size='350' side='right' caption='Class II ribonucleotide reductase dimer complex with dATP, UDP and Mg+2 ion (green) (PDB entry [[1xjg]])' scene='46/461381/Cv/1'>
+== Function ==
-'''Ribonucleotide reductase''' (RNR) catalyzes the formation of deoxyribonucleotides from ribonucleotides.  The RNR is a tetramer composed from large (RNR1) and small (RNR2) subunits.  Thymidine triphosphate (TTP) is an effector in the reaction.   For details on human RNR2 see [[P53R2]].
+'''Ribonucleotide reductase''' (RNR) or '''ribonucleotide-diphosphate reductase''' catalyzes the formation of deoxyribonucleotides from ribonucleotides<ref>PMID:16756507</ref>.  There are 3 classes of RNR.<br />
+*  '''Class Ia RNR''' is a tetramer composed from large (RNR1) and small (RNR2) subunits.  Class I RNR is iron-dependent and produces tyrosyl radical.  Thimidine triphosphate (TTP) is an effector in the reaction<ref>PMID:21456967</ref>.<br />
-{{TOC limit|limit=2}}
+*  ''' Class Ib RNR''' contains 2 proteins: α (NrdE) and β (NrdF)<ref>PMID:21250660</ref>.<br />
+''E. Coli'' contains two types of RNR: the aerobic RNR belongs to class Ia and is composed of proteins R1 and R2, the anaerobic RNR belongs to class Ib<ref>PMID:17496099</ref>.  <br />
-== 3D Structures of Ribonucletide reductase ==
+*  ''' Class II RNR''' reduces ribonucleotide triphosphates using coenzyme B12<ref>PMID:11875520</ref>.<br />
+*  '''Class III RNR''' generate glycine radical using S-adenosyl methionine and Fe-S center<ref>PMID:17606358</ref>.<br />
-===RNR large subunit===
+For details on human RNR2 see [[P53R2]].<br />
+For mouse RNR see [[Mouse Ribonucleotide Reductase R2]].<br />
-[[1zyz]], [[1zzd]], [[2cvs]], [[2cvt]], [[2cvu]], [[2cvv]], [[2cvw]], [[2cvx]], [[2cvy]] - yRNR R1 – yeast<BR />
+For RNR small subunit with nitrotyrosine modification see [[Nitrotyrosine]].<br />
-[[1pem]] - StRNR R1 - ''Salmonella typhimurium''<BR />
+See also [[Ribonucleotide Reductase]].
-[[5r1r]], [[6r1r]], [[7r1r]], [[1r1r]], [[1rlr]], [[1mrr]] - EcRNR R1 – ''Escherichia coli''
-===RNR large subunit complex===
-[[3hnc]] – hRNR M1 + TTP – human<BR />
-[[3hnd]] – hRNR M1 + GDP + TTP<BR />
-[[3hne]], [[3hnf]] – hRNR M1 + ATP + TTP<BR />
-[[2wgh]] - hRNR M1 + ATP + Mg<BR />
-[[3paw]] - yRNR R1 + ATP<BR />
-[[3k8t]] - yRNR R1 + ADP analog<BR />
-[[2zlf]], [[2zlg]] - yRNR R1 + peptide<BR />
-[[2eud]] - yRNR R1 + ligand<BR />
-[[1peo]], [[1peq]], [[2peu]] - StRNR R1 + effector<BR />
-[[2r1r]] - EcRNR R1 + TTP<BR />
-[[3r1r]] - EcRNR R1 + AMPPNP<BR />
-[[4r1r]] - EcRNR R1 + GDP + TTP<BR />
-===RNR small subunit===
-[[2xof]], [[3n37]], [[3n38]], [[2alx]], [[1piy]], [[1r65]], [[1mxr]], [[1jqc]], [[1jpr]], [[1av8]], [[1xik]], [[1rib]] – EcRNR R2 <BR />
-[[1yfd]], [[1piz]], [[1pj0]], [[1pj1]], [[1pm2]], [[1pim]], [[1piu]], [[1biq]], [[2av8]], [[1pfr]] - EcRNR R2 (mutant) <BR />
-[[3hf1]], [[2vux]], [[2uw2]] – hRNR M2<BR />
-[[3mjo]], [[3dhz]], [[1oqu]], [[1kgn]], [[1kgo]], [[1kgp]] – RNR R2 – ''Corynebacterium ammoniagenes''<BR />
-[[2p1i]] – RNR R2 – ''Plasmodium yoelii''<BR />
-[[2o1z]] - RNR R2 – ''Plasmodium vivax''<BR />
-[[1w68]], [[1h0n]], [[1h0o]], [[1xsm]] – mRNR R2 – mouse<BR />
-[[1smq]], [[1sms]] – yRNR 2<BR />
-[[1syy]] - CtRNR R2 – ''Chlamydia trachomatis''<BR />
-[[2ani]] - CtRNR R2 (mutant) <BR />
-[[1uz]]r – RNR R2 – ''Mycobacterium tuberculosis''<BR />
-[[1r2f]] - StRNR R2
-===RNR small subunit complex===
-[[1rsr]], [[1rsv]] - EcRNR R2 (mutant) + N3<BR />
-[[3n39]], [[3n3a]], [[3n3b]] – EcRNR R2 + NrdI<BR />
-[[1rnr]] – EcRNR R2 (mutant) + dopa<BR />
-[[1w69]] – mRNR R2 + acetate
-===RNR small+large subunit===
-[[2xak]], [[2xap]], [[2xo4]], [[2xo5]] - EcRNR R1+ R2 peptide<BR />
-[[2xav]], [[2xaw]], [[2xax]], [[2xay]], [[2xaz]], [[2x0x]] - EcRNR R1 (mutant) + R2 peptide<BR />
-[[2bq1]] - StRNR R1+ R2
-[[1xjf]] – TmRNR + ATP – ''Thermotoga maritima''<BR />
-[[1xjg]] - TmRNR + ATP-UDP<BR />
-[[1xjj]] - TmRNR + GTP<BR />
-[[1xjk]] - TmRNR + GTP-ADP<BR />
-[[1xjm]] - TmRNR + TTP<BR />
-[[1xje]] - TmRNR + TTP-GDP<BR />
-[[1xjn]] - TmRNR + ATP-CDP
+== Relevance ==
+RNR inhibitors are studied as therapeutic antiviral, antibacterial and anti-cancer drugs<ref>PMID:21791713</ref>.
+== Structural highlights ==
+Class II RNR is <scene name='46/461381/Cv/5'>vitamin B12-dependent</scene>. The active site which binds the substrate is in a tight pocket and contains conserved residues involved in the catalytic mechanism <ref>PMID:15475969</ref>.
+*<scene name='46/461381/Cv/6'>dATP binding site</scene>. Water molecules are shown as red spheres.
+*<scene name='46/461381/Cv/7'>UDP binding site</scene>.
+== 3D Structures of Ribonucleotide reductase ==
+[[Ribonucleotide reductase 3D structures]]
+</StructureSection>
+== References ==
+<references/>
 [[Category:Topic Page]]