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Ribonucleotide reductase: Difference between revisions

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{{STRUCTURE_1xjf| PDB=1xjf  | SIZE=350| SCENE= |right|CAPTION=Class III ribonucleotide reductase dimer complex with DTP (stick model) and Mg+2 ion (green), [[1xjf]] }}
<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.  There are 3 classes of RNR.<br />
'''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 I 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.<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 />
*  ''' Class II RNR''' reduces ribonucleotide triphosphates using coenzyme B12.<br />
*  ''' Class Ib RNR''' contains 2 proteins: α (NrdE) and β (NrdF)<ref>PMID:21250660</ref>.<br />
*  '''Class III RNR''' generate glycine radical using S-adenosyl methionine and Fe-S center.<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 />
*  ''' 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 />
For details on human RNR2 see [[P53R2]].<br />
For details on human RNR2 see [[P53R2]].<br />
For mouse RNR see [[Mouse Ribonucleotide Reductase R2]].<br />
For mouse RNR see [[Mouse Ribonucleotide Reductase R2]].<br />
For RNR small subunit with nitrolysine modification see [[Nitrolysine]].
For RNR small subunit with nitrotyrosine modification see [[Nitrotyrosine]].<br />
 
See also [[Ribonucleotide Reductase]].
== 3D Structures of Ribonucleotide reductase ==
 
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*'''Class I ribonucleotide reductase'''
 
*Ribonucleotide reductase large subunit
 
**[[1zyz]], [[1zzd]], [[2cvs]], [[2cvt]], [[2cvu]], [[2cvv]], [[2cvw]], [[2cvx]], [[2cvy]] - yRNR R1 – yeast<BR />
**[[5r1r]], [[6r1r]], [[7r1r]], [[1r1r]], [[1rlr]], [[1mrr]] - EcRNR R1 – ''Escherichia coli''<br />
**[[4n82]] – SsRNR – ''Streptococcus sanguinis''<br />
 
*''Ribonucleotide reductase 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 />
**[[3s87]] - yRNR R1 + ADP + GTP<br />
**[[3s8a]] - yRNR R1 (mutant) + GTP<br />
**[[3tba]] - yRNR R1 (mutant) + GTP + ADP<br />
**[[3s8b]] - yRNR R1 + AMPPNP + CDP<br />
**[[3s8c]], [[3tb9]] - yRNR R1 (mutant) + AMPPNP + CDP<br />
**[[2zlf]], [[2zlg]] - yRNR R1 + peptide<BR />
**[[2eud]] - yRNR R1 + ligand<BR />
**[[3rsr]] – yRNR + inhibitor<br />
**[[2r1r]] - EcRNR R1 + TTP<BR />
**[[3r1r]] - EcRNR R1 + AMPPNP<BR />
**[[4r1r]] - EcRNR R1 + GDP + TTP<BR />
**[[1qfn]] - EcRNR R1 + glutaredoxin 1<br />
**[[1peu]] - StRNR + DTP - ''Salmonella typhimurium''<br />
 
*RNR small subunit
 
**[[2xof]], [[3n37]], [[3n38]], [[2alx]], [[1piy]], [[1r65]], [[1mxr]], [[1jqc]], [[1jpr]], [[1av8]], [[1xik]], [[1rib]], [[4m1f]] – EcRNR R2 <BR />
**[[1yfd]], [[1piz]], [[1pj0]], [[1pj1]], [[1pm2]], [[1pim]], [[1piu]], [[1biq]], [[2av8]], [[1pfr]] - EcRNR R2 (mutant) <BR />
**[[3hf1]], [[2vux]], [[2uw2]], [[4djn]] – 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 />
**[[4d8f]], [[4d8g]], [[4m1i]] - CtRNR R2 + Fe + Mn<br />
**[[1syy]] - CtRNR R2 + Fe + Pb– ''Chlamydia trachomatis''<BR />
**[[2ani]] - CtRNR R2 (mutant) + Fe + Pb<BR />
**[[4m1h]] - CtRNR R2 <br />
**[[4dr0]] - RNR + Mn – Bacillus subtilis<br />
**[[1uzr]] – RNR R2 – ''Mycobacterium tuberculosis''<BR />
**[[3olj]] – hRNR M2<br />
**[[1jk0]] – yRNR Y2+Y4<br />
**[[3vpm]], [[3vpn]], [[3vpo]] – hRNR M2 (mutant)<br />
**[[2rcc]] – RNR – ''Bacillus halodurans''<br />
**[[4bmq]], [[4bmr]], [[4bmt]] - BcRNR + Fe – ''Bacillus cereus''<br />
**[[4bmu]] - BcRNR + Mn<br />
**[[4n83]] - SsRNR + Mn<br />
 
*''Ribonucleotide reductase 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<br />
**[[4bmo]], [[4bmp]] - BcRNR + NRDI <br />
 
*Ribonucleotide reductase small+large subunit
 
**[[3uus]], [[4erm]] - EcRNR R1+ R2<br />
**[[4erp]] - EcRNR R1+ R2 + inhibitor<br />
**[[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
 
*'''Class II ribonucleotide reductase'''
 
**[[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<br />
**[[3o0n]] - TmRNR + TTP + Co + Mg + deoxyadenosine + B12<br />
**[[3o0o]] - TmRNR + TTP + GDP + Mg + deoxyadenosine + B12<br />
**[[3o0q]] - TmRNR + TTP + GDP + Mg + adenosine <br />
**[[1pem]] - StRNR R1 <BR />
**[[1r2f]], [[2r2f]] - StRNR R2<br />
**[[1peo]], [[1peq]], [[2peu]] - StRNR R1 + effector<BR />
**[[1l1l]] – RNR (mutant) – ''Lactobacillus leichmannii''<br />
 
*'''Class III ribonucleotide reductase'''
 
**[[1h78]], [[1h79]], [[1h7a]], [[1hk8]] – T4RNR (mutant) + nucleotide triphosphate – bacteriophage T4<br />
**[[1h7b]] – T4RNR (mutant)  <br />
}}
 


== 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]]
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

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