Structural Basis for Activation of Class Ib Ribonucleotide Reductase

Overview

Journal Science

Specialty Science

Date 2010 Aug 7

PMID 20688982

Citations 78

Authors

Amie K Boal

Joseph A Cotruvo Jr

JoAnne Stubbe

Amy C Rosenzweig

Affiliations

Soon will be listed here.

Abstract

The class Ib ribonucleotide reductase of Escherichia coli can initiate reduction of nucleotides to deoxynucleotides with either a Mn(III)2-tyrosyl radical (Y•) or a Fe(III)2-Y• cofactor in the NrdF subunit. Whereas Fe(III)2-Y• can self-assemble from Fe(II)2-NrdF and O2, activation of Mn(II)2-NrdF requires a reduced flavoprotein, NrdI, proposed to form the oxidant for cofactor assembly by reduction of O2. The crystal structures reported here of E. coli Mn(II)2-NrdF and Fe(II)2-NrdF reveal different coordination environments, suggesting distinct initial binding sites for the oxidants during cofactor activation. In the structures of Mn(II)2-NrdF in complex with reduced and oxidized NrdI, a continuous channel connects the NrdI flavin cofactor to the NrdF Mn(II)2 active site. Crystallographic detection of a putative peroxide in this channel supports the proposed mechanism of Mn(III)2-Y• cofactor assembly.

Citing Articles

O Activation and Enzymatic C-H Bond Activation Mediated by a Dimanganese Cofactor.

Liu C, Rao G, Nguyen J, Britt R, Rittle J J Am Chem Soc. 2025; 147(2):2148-2157.

PMID: 39741465 PMC: 11819613. DOI: 10.1021/jacs.4c16271.

Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.

Capdevila D, Rondon J, Edmonds K, Rocchio J, Villarruel Dujovne M, Giedroc D Chem Rev. 2024; 124(24):13574-13659.

PMID: 39658019 PMC: 11672702. DOI: 10.1021/acs.chemrev.4c00264.

Structural insights into the initiation of free radical formation in the Class Ib ribonucleotide reductases in Mycobacteria.

Yadav L, Sharma V, Shanmugam M, Mande S Curr Res Struct Biol. 2024; 8:100157.

PMID: 39399574 PMC: 11470190. DOI: 10.1016/j.crstbi.2024.100157.

Class Ib Ribonucleotide Reductases: Activation of a Peroxido-MnMn to Generate a Reactive Oxo-MnMn Oxidant.

Doyle L, Magherusan A, Xu S, Murphy K, Farquhar E, Molton F Inorg Chem. 2024; 63(4):2194-2203.

PMID: 38231137 PMC: 10828993. DOI: 10.1021/acs.inorgchem.3c04163.

Homologous acetone carboxylases select Fe(II) or Mn(II) as the catalytic cofactor.

Shisler K, Kincannon W, Mattice J, Larson J, Valaydon-Pillay A, Mus F mBio. 2023; 15(2):e0298723.

PMID: 38126751 PMC: 10865871. DOI: 10.1128/mbio.02987-23.

References

Cotruvo Jr J, Stubbe J . NrdI, a flavodoxin involved in maintenance of the diferric-tyrosyl radical cofactor in Escherichia coli class Ib ribonucleotide reductase. Proc Natl Acad Sci U S A. 2008; 105(38):14383-8. PMC: 2567162. DOI: 10.1073/pnas.0807348105. View

Eklund H, Uhlin U, Farnegardh M, Logan D, Nordlund P . Structure and function of the radical enzyme ribonucleotide reductase. Prog Biophys Mol Biol. 2002; 77(3):177-268. DOI: 10.1016/s0079-6107(01)00014-1. View

Willing A, Follmann H, Auling G . Ribonucleotide reductase of Brevibacterium ammoniagenes is a manganese enzyme. Eur J Biochem. 1988; 170(3):603-11. DOI: 10.1111/j.1432-1033.1988.tb13740.x. View

Do L, Hayashi T, Moenne-Loccoz P, Lippard S . Carboxylate as the protonation site in (Peroxo)diiron(III) model complexes of soluble methane monooxygenase and related diiron proteins. J Am Chem Soc. 2010; 132(4):1273-5. PMC: 2812653. DOI: 10.1021/ja909718f. View

Sazinsky M, Lippard S . Product bound structures of the soluble methane monooxygenase hydroxylase from Methylococcus capsulatus (Bath): protein motion in the alpha-subunit. J Am Chem Soc. 2005; 127(16):5814-25. DOI: 10.1021/ja044099b. View

Rohr A, Hersleth H, Andersson K . Tracking flavin conformations in protein crystal structures with Raman spectroscopy and QM/MM calculations. Angew Chem Int Ed Engl. 2010; 49(13):2324-7. DOI: 10.1002/anie.200907143. View

Drennan C, Pattridge K, WEBER C, Metzger A, Hoover D, Ludwig M . Refined structures of oxidized flavodoxin from Anacystis nidulans. J Mol Biol. 1999; 294(3):711-24. DOI: 10.1006/jmbi.1999.3151. View

Gon S, Faulkner M, Beckwith J . In vivo requirement for glutaredoxins and thioredoxins in the reduction of the ribonucleotide reductases of Escherichia coli. Antioxid Redox Signal. 2006; 8(5-6):735-42. DOI: 10.1089/ars.2006.8.735. View

Sazinsky M, Lippard S . Correlating structure with function in bacterial multicomponent monooxygenases and related diiron proteins. Acc Chem Res. 2006; 39(8):558-66. DOI: 10.1021/ar030204v. View

10.

Roca I, Torrents E, Sahlin M, Gibert I, Sjoberg B . NrdI essentiality for class Ib ribonucleotide reduction in Streptococcus pyogenes. J Bacteriol. 2008; 190(14):4849-58. PMC: 2447006. DOI: 10.1128/JB.00185-08. View

11.

Hogbom M, Huque Y, Sjoberg B, Nordlund P . Crystal structure of the di-iron/radical protein of ribonucleotide reductase from Corynebacterium ammoniagenes. Biochemistry. 2002; 41(4):1381-9. DOI: 10.1021/bi011429l. View

12.

McHugh J, Rodriguez-Quinones F, Abdul-Tehrani H, Svistunenko D, Poole R, Cooper C . Global iron-dependent gene regulation in Escherichia coli. A new mechanism for iron homeostasis. J Biol Chem. 2003; 278(32):29478-86. DOI: 10.1074/jbc.M303381200. View

13.

Cox N, Ogata H, Stolle P, Reijerse E, Auling G, Lubitz W . A tyrosyl-dimanganese coupled spin system is the native metalloradical cofactor of the R2F subunit of the ribonucleotide reductase of Corynebacterium ammoniagenes. J Am Chem Soc. 2010; 132(32):11197-213. DOI: 10.1021/ja1036995. View

14.

Eriksson M, Jordan A, Eklund H . Structure of Salmonella typhimurium nrdF ribonucleotide reductase in its oxidized and reduced forms. Biochemistry. 1998; 37(38):13359-69. DOI: 10.1021/bi981380s. View

15.

Zhou Z, Swenson R . Electrostatic effects of surface acidic amino acid residues on the oxidation-reduction potentials of the flavodoxin from Desulfovibrio vulgaris (Hildenborough). Biochemistry. 1995; 34(10):3183-92. DOI: 10.1021/bi00010a007. View

16.

Uppsten M, Farnegardh M, Domkin V, Uhlin U . The first holocomplex structure of ribonucleotide reductase gives new insight into its mechanism of action. J Mol Biol. 2006; 359(2):365-77. DOI: 10.1016/j.jmb.2006.03.035. View

17.

Atta M, Nordlund P, Aberg A, Eklund H, Fontecave M . Substitution of manganese for iron in ribonucleotide reductase from Escherichia coli. Spectroscopic and crystallographic characterization. J Biol Chem. 1992; 267(29):20682-8. View

18.

Jurado J, Prieto-Alamo M, Holmgren A, Pueyo C . Expression analysis of the nrdHIEF operon from Escherichia coli. Conditions that trigger the transcript level in vivo. J Biol Chem. 2001; 276(21):18031-7. DOI: 10.1074/jbc.M011728200. View

19.

Barynin V, Whittaker M, Antonyuk S, Lamzin V, Harrison P, Artymiuk P . Crystal structure of manganese catalase from Lactobacillus plantarum. Structure. 2001; 9(8):725-38. DOI: 10.1016/s0969-2126(01)00628-1. View

20.

Huque Y, Fieschi F, Torrents E, Gibert I, Eliasson R, REICHARD P . The active form of the R2F protein of class Ib ribonucleotide reductase from Corynebacterium ammoniagenes is a diferric protein. J Biol Chem. 2000; 275(33):25365-71. DOI: 10.1074/jbc.M002751200. View