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Structural mechanism of allosteric substrate specificity regulation in a ribonucleotide reductase.

Larsson KM, Jordan A, Eliasson R, Reichard P, Logan DT, Nordlund P
Nat Struct Mol Biol 11 1142-9 (2004)
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Cited: 61 times
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Abstract

Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides into deoxyribonucleotides, which constitute the precursor pools used for DNA synthesis and repair. Imbalances in these pools increase mutational rates and are detrimental to the cell. Balanced precursor pools are maintained primarily through the regulation of the RNR substrate specificity. Here, the molecular mechanism of the allosteric substrate specificity regulation is revealed through the structures of a dimeric coenzyme B12-dependent RNR from Thermotoga maritima, both in complexes with four effector-substrate nucleotide pairs and in three complexes with only effector. The mechanism is based on the flexibility of loop 2, a key structural element, which forms a bridge between the specificity effector and substrate nucleotides. Substrate specificity is achieved as different effectors and their cognate substrates stabilize specific discrete loop 2 conformations. The mechanism of substrate specificity regulation is probably general for most class I and class II RNRs.

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Reviews citing this publication (10)

  1. Ribonucleotide reductases. Nordlund P, Reichard P. Annu Rev Biochem 75 681-706 (2006)
  2. DNA building blocks: keeping control of manufacture. Hofer A, Crona M, Logan DT, Sjöberg BM. Crit Rev Biochem Mol Biol 47 50-63 (2012)
  3. The origin and evolution of ribonucleotide reduction. Lundin D, Berggren G, Logan DT, Sjöberg BM. Life (Basel) 5 604-636 (2015)
  4. Metal use in ribonucleotide reductase R2, di-iron, di-manganese and heterodinuclear--an intricate bioinorganic workaround to use different metals for the same reaction. Högbom M. Metallomics 3 110-120 (2011)
  5. Ribonucleotide reductases: influence of environment on synthesis and activity. Gon S, Beckwith J. Antioxid Redox Signal 8 773-780 (2006)
  6. The structural basis for the allosteric regulation of ribonucleotide reductase. Ahmad MF, Dealwis CG. Prog Mol Biol Transl Sci 117 389-410 (2013)
  7. Current knowledge and recent advances in understanding metabolism of the model cyanobacterium Synechocystis sp. PCC 6803. Mills LA, McCormick AJ, Lea-Smith DJ. Biosci Rep 40 BSR20193325 (2020)
  8. The prototypic class Ia ribonucleotide reductase from Escherichia coli: still surprising after all these years. Brignole EJ, Ando N, Zimanyi CM, Drennan CL. Biochem Soc Trans 40 523-530 (2012)
  9. Functional organization of human SAMHD1 and mechanisms of HIV-1 restriction. Ahn J. Biol Chem 397 373-379 (2016)
  10. Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present. Huff SE, Winter JM, Dealwis CG. Biomolecules 12 815 (2022)

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  1. Tight interplay among SAMHD1 protein level, cellular dNTP levels, and HIV-1 proviral DNA synthesis kinetics in human primary monocyte-derived macrophages. Kim B, Nguyen LA, Daddacha W, Hollenbaugh JA. J Biol Chem 287 21570-21574 (2012)
  2. Mechanisms of mutagenesis in vivo due to imbalanced dNTP pools. Kumar D, Abdulovic AL, Viberg J, Nilsson AK, Kunkel TA, Chabes A. Nucleic Acids Res 39 1360-1371 (2011)
  3. Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint. Kumar D, Viberg J, Nilsson AK, Chabes A. Nucleic Acids Res 38 3975-3983 (2010)
  4. Regulation of nucleotide metabolism by mutant p53 contributes to its gain-of-function activities. Kollareddy M, Dimitrova E, Vallabhaneni KC, Chan A, Le T, Chauhan KM, Carrero ZI, Ramakrishnan G, Watabe K, Haupt Y, Haupt S, Pochampally R, Boss GR, Romero DG, Radu CG, Martinez LA. Nat Commun 6 7389 (2015)
  5. Nucleoside salvage pathway kinases regulate hematopoiesis by linking nucleotide metabolism with replication stress. Austin WR, Armijo AL, Campbell DO, Singh AS, Hsieh T, Nathanson D, Herschman HR, Phelps ME, Witte ON, Czernin J, Radu CG. J Exp Med 209 2215-2228 (2012)
  6. Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation. Xu H, Faber C, Uchiki T, Fairman JW, Racca J, Dealwis C. Proc Natl Acad Sci U S A 103 4022-4027 (2006)
  7. Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene. Bornstein B, Area E, Flanigan KM, Ganesh J, Jayakar P, Swoboda KJ, Coku J, Naini A, Shanske S, Tanji K, Hirano M, DiMauro S. Neuromuscul Disord 18 453-459 (2008)
  8. Modern mRNA proofreading and repair: clues that the last universal common ancestor possessed an RNA genome? Poole AM, Logan DT. Mol Biol Evol 22 1444-1455 (2005)
  9. Ribonucleotide reduction - horizontal transfer of a required function spans all three domains. Lundin D, Gribaldo S, Torrents E, Sjöberg BM, Poole AM. BMC Evol Biol 10 383 (2010)
  10. Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli. Zimanyi CM, Chen PY, Kang G, Funk MA, Drennan CL. Elife 5 e07141 (2016)
  11. Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly. Xu H, Faber C, Uchiki T, Racca J, Dealwis C. Proc Natl Acad Sci U S A 103 4028-4033 (2006)
  12. Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit. Rozman Grinberg I, Lundin D, Hasan M, Crona M, Jonna VR, Loderer C, Sahlin M, Markova N, Borovok I, Berggren G, Hofer A, Logan DT, Sjöberg BM. Elife 7 e31529 (2018)
  13. Novel mutator mutants of E. coli nrdAB ribonucleotide reductase: insight into allosteric regulation and control of mutation rates. Ahluwalia D, Bienstock RJ, Schaaper RM. DNA Repair (Amst) 11 480-487 (2012)
  14. Hypermutability and error catastrophe due to defects in ribonucleotide reductase. Ahluwalia D, Schaaper RM. Proc Natl Acad Sci U S A 110 18596-18601 (2013)
  15. 3.3-Å resolution cryo-EM structure of human ribonucleotide reductase with substrate and allosteric regulators bound. Brignole EJ, Tsai KL, Chittuluru J, Li H, Aye Y, Penczek PA, Stubbe J, Drennan CL, Asturias F. Elife 7 e31502 (2018)
  16. Determination of the in vivo stoichiometry of tyrosyl radical per betabeta' in Saccharomyces cerevisiae ribonucleotide reductase. Ortigosa AD, Hristova D, Perlstein DL, Zhang Z, Huang M, Stubbe J. Biochemistry 45 12282-12294 (2006)
  17. Structural Mechanism of Allosteric Activity Regulation in a Ribonucleotide Reductase with Double ATP Cones. Johansson R, Jonna VR, Kumar R, Nayeri N, Lundin D, Sjöberg BM, Hofer A, Logan DT. Structure 24 906-917 (2016)
  18. The class III ribonucleotide reductase from Neisseria bacilliformis can utilize thioredoxin as a reductant. Wei Y, Funk MA, Rosado LA, Baek J, Drennan CL, Stubbe J. Proc Natl Acad Sci U S A 111 E3756-65 (2014)
  19. An endogenous dAMP ligand in Bacillus subtilis class Ib RNR promotes assembly of a noncanonical dimer for regulation by dATP. Parker MJ, Maggiolo AO, Thomas WC, Kim A, Meisburger SP, Ando N, Boal AK, Stubbe J. Proc Natl Acad Sci U S A 115 E4594-E4603 (2018)
  20. E2F4 and ribonucleotide reductase mediate S-phase arrest in colon cancer cells treated with chlorophyllin. Chimploy K, Díaz GD, Li Q, Carter O, Dashwood WM, Mathews CK, Williams DE, Bailey GS, Dashwood RH. Int J Cancer 125 2086-2094 (2009)
  21. Potent competitive inhibition of human ribonucleotide reductase by a nonnucleoside small molecule. Ahmad MF, Alam I, Huff SE, Pink J, Flanagan SA, Shewach D, Misko TA, Oleinick NL, Harte WE, Viswanathan R, Harris ME, Dealwis CG. Proc Natl Acad Sci U S A 114 8241-8246 (2017)
  22. Role of arginine 293 and glutamine 288 in communication between catalytic and allosteric sites in yeast ribonucleotide reductase. Ahmad MF, Kaushal PS, Wan Q, Wijerathna SR, An X, Huang M, Dealwis CG. J Mol Biol 419 315-329 (2012)
  23. Substrate Specificity of SAMHD1 Triphosphohydrolase Activity Is Controlled by Deoxyribonucleoside Triphosphates and Phosphorylation at Thr592. Jang S, Zhou X, Ahn J. Biochemistry 55 5635-5646 (2016)
  24. A Ferredoxin Disulfide Reductase Delivers Electrons to the Methanosarcina barkeri Class III Ribonucleotide Reductase. Wei Y, Li B, Prakash D, Ferry JG, Elliott SJ, Stubbe J. Biochemistry 54 7019-7028 (2015)
  25. Proteomics analysis of Thermoplasma acidophilum with a focus on protein complexes. Sun N, Beck F, Knispel RW, Siedler F, Scheffer B, Nickell S, Baumeister W, Nagy I. Mol Cell Proteomics 6 492-502 (2007)
  26. Identification of Non-nucleoside Human Ribonucleotide Reductase Modulators. Ahmad MF, Huff SE, Pink J, Alam I, Zhang A, Perry K, Harris ME, Misko T, Porwal SK, Oleinick NL, Miyagi M, Viswanathan R, Dealwis CG. J Med Chem 58 9498-9509 (2015)
  27. The case for an early biological origin of DNA. Poole AM, Horinouchi N, Catchpole RJ, Si D, Hibi M, Tanaka K, Ogawa J. J Mol Evol 79 204-212 (2014)
  28. Structure-Guided Synthesis and Mechanistic Studies Reveal Sweetspots on Naphthyl Salicyl Hydrazone Scaffold as Non-Nucleosidic Competitive, Reversible Inhibitors of Human Ribonucleotide Reductase. Huff SE, Mohammed FA, Yang M, Agrawal P, Pink J, Harris ME, Dealwis CG, Viswanathan R. J Med Chem 61 666-680 (2018)
  29. A Novel One-Pot Enzyme Cascade for the Biosynthesis of Cladribine Triphosphate. Frisch J, Maršić T, Loderer C. Biomolecules 11 346 (2021)
  30. A unique cysteine-rich zinc finger domain present in a majority of class II ribonucleotide reductases mediates catalytic turnover. Loderer C, Jonna VR, Crona M, Rozman Grinberg I, Sahlin M, Hofer A, Lundin D, Sjöberg BM. J Biol Chem 292 19044-19054 (2017)
  31. Comment Closing the circle on ribonucleotide reductases. Logan DT. Nat Struct Mol Biol 18 251-253 (2011)
  32. Targeting the Large Subunit of Human Ribonucleotide Reductase for Cancer Chemotherapy. Wijerathna SR, Ahmad MF, Xu H, Fairman JW, Zhang A, Kaushal PS, Wan Q, Kiser J, Dealwis CG. Pharmaceuticals (Basel) 4 1328-1354 (2011)
  33. The Crystal Structure of Thermotoga maritima Class III Ribonucleotide Reductase Lacks a Radical Cysteine Pre-Positioned in the Active Site. Aurelius O, Johansson R, Bågenholm V, Lundin D, Tholander F, Balhuizen A, Beck T, Sahlin M, Sjöberg BM, Mulliez E, Logan DT. PLoS One 10 e0128199 (2015)
  34. The equilibrative nucleoside transporter ENT1 is critical for nucleotide homeostasis and optimal erythropoiesis. Mikdar M, González-Menéndez P, Cai X, Zhang Y, Serra M, Dembele AK, Boschat AC, Sanquer S, Chhuon C, Guerrera IC, Sitbon M, Hermine O, Colin Y, Le Van Kim C, Kinet S, Mohandas N, Xia Y, Peyrard T, Taylor N, Azouzi S. Blood 137 3548-3562 (2021)
  35. Class Id ribonucleotide reductase utilizes a Mn2(IV,III) cofactor and undergoes large conformational changes on metal loading. Rozman Grinberg I, Berglund S, Hasan M, Lundin D, Ho FM, Magnuson A, Logan DT, Sjöberg BM, Berggren G. J Biol Inorg Chem 24 863-877 (2019)
  36. Evaluating the therapeutic potential of a non-natural nucleotide that inhibits human ribonucleotide reductase. Ahmad MF, Wan Q, Jha S, Motea E, Berdis A, Dealwis C. Mol Cancer Ther 11 2077-2086 (2012)
  37. The enantioselectivities of the active and allosteric sites of mammalian ribonucleotide reductase. He J, Roy B, Périgaud C, Kashlan OB, Cooperman BS. FEBS J 272 1236-1242 (2005)
  38. Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade. Burnim AA, Spence MA, Xu D, Jackson CJ, Ando N. Elife 11 e79790 (2022)
  39. Inactivation of Lactobacillus leichmannii ribonucleotide reductase by 2',2'-difluoro-2'-deoxycytidine 5'-triphosphate: adenosylcobalamin destruction and formation of a nucleotide-based radical. Lohman GJ, Gerfen GJ, Stubbe J. Biochemistry 49 1396-1403 (2010)
  40. Non-host class II ribonucleotide reductase in Thermus viruses: sequence adaptation and host interaction. Loderer C, Holmfeldt K, Lundin D. PeerJ 7 e6700 (2019)
  41. Structural and Biochemical Investigation of Class I Ribonucleotide Reductase from the Hyperthermophile Aquifex aeolicus. Rehling D, Scaletti ER, Rozman Grinberg I, Lundin D, Sahlin M, Hofer A, Sjöberg BM, Stenmark P. Biochemistry 61 92-106 (2022)
  42. The translational repressor 4E-BP1 regulates RRM2 levels and functions as a tumor suppressor in Ewing sarcoma tumors. Goss KL, Koppenhafer SL, Waters T, Terry WW, Wen KK, Wu M, Ostergaard J, Gordon PM, Gordon DJ. Oncogene 40 564-577 (2021)
  43. Analysis of insertions and extensions in the functional evolution of the ribonucleotide reductase family. Burnim AA, Xu D, Spence MA, Jackson CJ, Ando N. Protein Sci 31 e4483 (2022)
  44. Hierarchical classification of functionally equivalent genes in prokaryotes. Wu H, Mao F, Olman V, Xu Y. Nucleic Acids Res 35 2125-2140 (2007)
  45. Letter Inhibition of yeast ribonucleotide reductase by Sml1 depends on the allosteric state of the enzyme. Misko TA, Wijerathna SR, Radivoyevitch T, Berdis AJ, Ahmad MF, Harris ME, Dealwis CG. FEBS Lett 590 1704-1712 (2016)
  46. Utilization of cobalamin is ubiquitous in early-branching fungal phyla. Orłowska M, Steczkiewicz K, Muszewska A. Genome Biol Evol 13 evab043 (2021)
  47. Bacillus halodurans Strain C125 Encodes and Synthesizes Enzymes from Both Known Pathways To Form dUMP Directly from Cytosine Deoxyribonucleotides. Oehlenschlæger CB, Løvgreen MN, Reinauer E, Lehtinen E, Pind ML, Harris P, Martinussen J, Willemoës M. Appl Environ Microbiol 81 3395-3404 (2015)
  48. Phylogenetic sequence analysis and functional studies reveal compensatory amino acid substitutions in loop 2 of human ribonucleotide reductase. Knappenberger AJ, Grandhi S, Sheth R, Ahmad MF, Viswanathan R, Harris ME. J Biol Chem 292 16463-16476 (2017)
  49. Structural determinants and distribution of phosphate specificity in ribonucleotide reductases. Schell E, Nouairia G, Steiner E, Weber N, Lundin D, Loderer C. J Biol Chem 297 101008 (2021)
  50. A rapid and sensitive assay for quantifying the activity of both aerobic and anaerobic ribonucleotide reductases acting upon any or all substrates. Levitz TS, Andree GA, Jonnalagadda R, Dawson CD, Bjork RE, Drennan CL. PLoS One 17 e0269572 (2022)


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