Ribonucleotide reductase

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Revision as of 09:50, 16 December 2019

spinqualitylabelsall models Class II ribonucleotide reductase dimer complex with dATP, UDP and Mg+2 ion (green) (PDB entry 1xjg) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 Structural highlights 4 3D Structures of Ribonucleotide reductase Function Ribonucleotide reductase (RNR) or ribonucleotide-diphosphate reductase catalyzes the formation of deoxyribonucleotides from ribonucleotides[1]. There are 3 classes of RNR. 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[2]. Class Ib RNR contains 2 proteins: α (NrdE) and β (NrdF)[3]. 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[4]. Class II RNR reduces ribonucleotide triphosphates using coenzyme B12[5]. Class III RNR generate glycine radical using S-adenosyl methionine and Fe-S center[6]. For details on human RNR2 see P53R2. For mouse RNR see Mouse Ribonucleotide Reductase R2. For RNR small subunit with nitrotyrosine modification see Nitrotyrosine. Relevance RNR inhibitors are studied as therapeutic antiviral, antibacterial and anti-cancer drugs[7]. Structural highlights Class II RNR is . The active site which binds the substrate is in a tight pocket and contains conserved residues involved in the catalytic mechanism [8]. . Water molecules are shown as red spheres. . 3D Structures of Ribonucleotide reductase Ribonucleotide reductase 3D structures

References

1. ↑ Nordlund P, Reichard P. Ribonucleotide reductases. Annu Rev Biochem. 2006;75:681-706. PMID:16756507 doi:http://dx.doi.org/10.1146/annurev.biochem.75.103004.142443
2. ↑ Cotruvo JA, Stubbe J. Class I ribonucleotide reductases: metallocofactor assembly and repair in vitro and in vivo. Annu Rev Biochem. 2011;80:733-67. doi: 10.1146/annurev-biochem-061408-095817. PMID:21456967 doi:http://dx.doi.org/10.1146/annurev-biochem-061408-095817
3. ↑ Cotruvo JA, Stubbe J. Escherichia coli class Ib ribonucleotide reductase contains a dimanganese(III)-tyrosyl radical cofactor in vivo. Biochemistry. 2011 Mar 15;50(10):1672-81. doi: 10.1021/bi101881d. Epub 2011 Feb, 15. PMID:21250660 doi:http://dx.doi.org/10.1021/bi101881d
4. ↑ Torrents E, Grinberg I, Gorovitz-Harris B, Lundstrom H, Borovok I, Aharonowitz Y, Sjoberg BM, Cohen G. NrdR controls differential expression of the Escherichia coli ribonucleotide reductase genes. J Bacteriol. 2007 Jul;189(14):5012-21. Epub 2007 May 11. PMID:17496099 doi:http://dx.doi.org/JB.00440-07
5. ↑ Sintchak MD, Arjara G, Kellogg BA, Stubbe J, Drennan CL. The crystal structure of class II ribonucleotide reductase reveals how an allosterically regulated monomer mimics a dimer. Nat Struct Biol. 2002 Apr;9(4):293-300. PMID:11875520 doi:http://dx.doi.org/10.1038/nsb774
6. ↑ Kirdis E, Jonsson IM, Kubica M, Potempa J, Josefsson E, Masalha M, Foster SJ, Tarkowski A. Ribonucleotide reductase class III, an essential enzyme for the anaerobic growth of Staphylococcus aureus, is a virulence determinant in septic arthritis. Microb Pathog. 2007 Nov-Dec;43(5-6):179-88. doi: 10.1016/j.micpath.2007.05.008., Epub 2007 May 25. PMID:17606358 doi:http://dx.doi.org/10.1016/j.micpath.2007.05.008
7. ↑ Munro JB, Silva JC. Ribonucleotide reductase as a target to control apicomplexan diseases. Curr Issues Mol Biol. 2012;14(1):9-26. Epub 2011 Jul 26. PMID:21791713
8. ↑ Larsson KM, Jordan A, Eliasson R, Reichard P, Logan DT, Nordlund P. Structural mechanism of allosteric substrate specificity regulation in a ribonucleotide reductase. Nat Struct Mol Biol. 2004 Nov;11(11):1142-9. Epub 2004 Oct 10. PMID:15475969 doi:http://dx.doi.org/10.1038/nsmb838