The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Reversible, Long-Range Radical Transfer in E. coli Class Ia Ribonucleotide Reductase
Open accessAbstract
Ribonucleotide reductases (RNRs) catalyze the conversionof nucleotides to 2'-deoxynucleotides and are classified on the basis of the metallo-cofactor used to conduct this chemistry. The class Ia RNRs initiate nucleotide reduction when a stable diferric-tyrosyl radical (Y•, t1/2 of 4 days at 4 °C) cofactor in the β2 subunit transiently oxidizes a cysteine to a thiyl radical (S•) in the active site of the α2 subunit. In the active α2β2 complex of the class Ia RNR from E. coli , researchers have proposed that radical hopping occurs reversibly over 35 Å along a specific pathway comprised of redox-active aromatic amino acids: Y122• ↔ [W48?] ↔ Y356 in β2 to Y731 ↔ Y730 ↔ C439 in α2. Each step necessitates a proton-coupled electron transfer (PCET). Protein conformational changes constitute the rate-limiting step in the overall catalytic scheme and kinetically mask the detailed chemistry of the PCET steps. Technology has evolved to allow the site-selective replacement of the four pathway tyrosines with unnatural tyrosine analogues. Rapid kinetic techniques combined with multifrequency electron paramagnetic resonance, pulsed electron-electron double resonance, and electron nuclear double resonance spectroscopies have facilitated the analysis of stable and transient radical intermediates in these mutants. These studies are beginning to reveal the mechanistic underpinnings of the radical transfer (RT) process. This Account summarizes recent mechanistic studies on mutant E. coli RNRs containing the following tyrosine analogues: 3,4-dihydroxyphenylalanine (DOPA) or 3-aminotyrosine (NH2Y), both thermodynamic radical traps; 3-nitrotyrosine (NO2Y), a thermodynamic barrier and probe of local environmental perturbations to the phenolic pKa; and fluorotyrosines (FnYs, n = 2 or 3), dual reporters on local pKas and reduction potentials. These studies have established the existence of a specific pathway spanning 35 Å within a globular α2β2 complex that involves one stable (position 122) and three transient (positions 356, 730, and 731) Y•s. Our results also support that RT occurs by an orthogonal PCET mechanism within β2, with Y122• reduction accompanied by proton transfer from an Fe1-bound water in the diferric cluster and Y356 oxidation coupled to an off-pathway proton transfer likely involving E350. In α2, RT likely occurs by a co-linear PCET mechanism, based on studies of light-initiated radical propagation from photopeptides that mimic the β2 subunit to the intact α2 subunit and on [(2)H]-ENDOR spectroscopic analysis of the hydrogen-bonding environment surrounding a stabilized NH2Y• formed at position 730. Additionally, studies on the thermodynamics of the RT pathway reveal that the relative reduction potentials decrease according to Y122 < Y356 < Y731 ≈ Y730 ≤ C439, and that the pathway in the forward direction is thermodynamically unfavorable. C439 oxidation is likely driven by rapid, irreversible loss of water during the nucleotide reduction process. Kinetic studies of radical intermediates reveal that RT is gated by conformational changes that occur on the order of >100 s(-1) in addition to the changes that are rate-limiting in the wild-type enzyme (∼10 s(-1)). The rate constant of one of the PCET steps is ∼10(5) s(-1), as measured in photoinitiated experiments.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Protein Radicals in Enzyme Catalysis
Stubbe, J., & van der Donk, W. A. (1998) · Chemical Reviews · doi:10.1021/cr9400875 · Cited by 1,377
Self-citationPROTON-COUPLED ELECTRON TRANSFER
Cukier, R. I., & Nocera, D. G. (1998) · Annual Review of Physical Chemistry · doi:10.1146/annurev.physchem.49.1.337 · Cited by 854
Self-citationStubbe, J., Nocera, D. G., Yee, C. S., & Chang, M. C. Y. (2003) · Chemical Reviews · doi:10.1021/cr020421u · Cited by 823
Self-citationPROTON-COUPLED ELECTRON TRANSFER: A Reaction Chemist's View
Mayer, J. M. (2004) · Annual Review of Physical Chemistry · doi:10.1146/annurev.physchem.55.091602.094446 · Cited by 814
Structure of ribonucleotide reductase protein R1
Uhlin, U., & Eklund, H. (1994) · Nature · doi:10.1038/370533a0 · Cited by 573
Reece, S. Y., & Nocera, D. G. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.080207.092132 · Cited by 483
Self-citationReece, S. Y., Hodgkiss, J. M., Stubbe, J., & Nocera, D. G. (2006) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2006.1874 · Cited by 294
Self-citationCliment, I., Sjöberg, B., & Huang, C. (1992) · Biochemistry · doi:10.1021/bi00135a009 · Cited by 148
Seyedsayamdost, M. R., Xie, J., Chan, C. T. Y., Schultz, P. G., & Stubbe, J. (2007) · Journal of the American Chemical Society · doi:10.1021/ja076043y · Cited by 147
Self-citationSeyedsayamdost, M. R., Reece, S. Y., Nocera, D. G., & Stubbe, J. (2006) · Journal of the American Chemical Society · doi:10.1021/ja055926r · Cited by 144
Self-citationCliment, I., Sjöberg, B., & Huang, C. (1991) · Biochemistry · doi:10.1021/bi00235a008 · Cited by 127
Pre-Steady-State and Steady-State Kinetic Analysis of E. coli Class I Ribonucleotide Reductase
Ge, J., Yu, G., Ator, M. A., & Stubbe, J. (2003) · Biochemistry · doi:10.1021/bi034374r · Cited by 126
Self-citationSeyedsayamdost, M. R., Yee, C. S., Reece, S. Y., Nocera, D. G., & Stubbe, J. (2006) · Journal of the American Chemical Society · doi:10.1021/ja055927j · Cited by 123
Self-citationGerfen, G. J., Bellew, B. F., Un, S., Bollinger, J. M., Jr., Stubbe, J., Griffin, R. G., & Singel, D. J. (1993) · Journal of the American Chemical Society · doi:10.1021/ja00067a071 · Cited by 120
Self-citationBennati, M., Robblee, J. H., Mugnaini, V., Stubbe, J., Freed, J. H., & Borbat, P. P. (2005) · Journal of the American Chemical Society · doi:10.1021/ja054991y · Cited by 115
Self-citationMinnihan, E. C., Young, D. D., Schultz, P. G., & Stubbe, J. (2011) · Journal of the American Chemical Society · doi:10.1021/ja207719f · Cited by 109
Self-citationSeyedsayamdost, M. R., & Stubbe, J. (2006) · Journal of the American Chemical Society · doi:10.1021/ja057776q · Cited by 93
Self-citationMadej, E., & Wardman, P. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.03.002 · Cited by 87
Yee, C. S., Seyedsayamdost, M. R., Chang, M. C. Y., Nocera, D. G., & Stubbe, J. (2003) · Biochemistry · doi:10.1021/bi0352365 · Cited by 87
Self-citationYokoyama, K., Uhlin, U., & Stubbe, J. (2010) · Journal of the American Chemical Society · doi:10.1021/ja101097p · Cited by 85
Self-citationSeyedsayamdost, M. R., Chan, C. T. Y., Mugnaini, V., Stubbe, J., & Bennati, M. (2007) · Journal of the American Chemical Society · doi:10.1021/ja076459b · Cited by 77
Self-citationMinnihan, E. C., Seyedsayamdost, M. R., Uhlin, U., & Stubbe, J. (2011) · Journal of the American Chemical Society · doi:10.1021/ja201640n · Cited by 70
Self-citationWörsdörfer, B., Conner, D. A., Yokoyama, K., Livada, J., Seyedsayamdost, M. R., Jiang, W., Silakov, A., Stubbe, J., Bollinger, J. M., Jr., & Krebs, C. (2013) · Journal of the American Chemical Society · doi:10.1021/ja401342s · Cited by 68
Self-citationYokoyama, K., Smith, A. A., Corzilius, B., Griffin, R. G., & Stubbe, J. (2011) · Journal of the American Chemical Society · doi:10.1021/ja207455k · Cited by 67
Self-citationA Hot Oxidant, 3-NO2Y122 Radical, Unmasks Conformational Gating in Ribonucleotide Reductase
Yokoyama, K., Uhlin, U., & Stubbe, J. (2010) · Journal of the American Chemical Society · doi:10.1021/ja1069344 · Cited by 63
Self-citationYee, C. S., Chang, Ge, J., Nocera, D. G., & Stubbe, J. (2003) · Journal of the American Chemical Society · doi:10.1021/ja036242r · Cited by 62
Self-citationMechanistic Investigations of Ribonucleotide Reductases
Licht, S. L., & Stubbe, J. (1999) · Elsevier eBooks · doi:10.1016/b978-0-08-091283-7.00114-4 · Cited by 57
Self-citationArgirević, T., Riplinger, C., Stubbe, J., Neese, F., & Bennati, M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja3071682 · Cited by 53
Self-citationPhoto-ribonucleotide reductase β2 by selective cysteine labeling with a radical phototrigger
Pizano, A. A., Lutterman, D. A., Holder, P. G., Teets, T. S., Stubbe, J., & Nocera, D. G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1115778108 · Cited by 53
Self-citationMinnihan, E. C., Ando, N., Brignole, E. J., Olshansky, L., Chittuluru, J. R., Asturias, F. J., Drennan, C. L., Nocera, D. G., & Stubbe, J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220691110 · Cited by 50
Self-citationReece, S. Y., Seyedsayamdost, M. R., Stubbe, J., & Nocera, D. G. (2007) · Journal of the American Chemical Society · doi:10.1021/ja0704434 · Cited by 49
Self-citationDeciphering Radical Transport in the Large Subunit of Class I Ribonucleotide Reductase
Holder, P. G., Pizano, A. A., Anderson, B. L., Stubbe, J., & Nocera, D. G. (2011) · Journal of the American Chemical Society · doi:10.1021/ja209016j · Cited by 44
Self-citationSeyedsayamdost, M. R., Argirević, T., Minnihan, E. C., Stubbe, J., & Bennati, M. (2009) · Journal of the American Chemical Society · doi:10.1021/ja903879w · Cited by 27
Self-citationMinnihan, E. C., Seyedsayamdost, M. R., & Stubbe, J. (2009) · Biochemistry · doi:10.1021/bi901439w · Cited by 22
Self-citation
Cited by
Biochemistry and Theory of Proton-Coupled Electron Transfer
Migliore, A., Polizzi, N. F., Therien, M. J., & Beratan, D. N. (2014) · Chemical Reviews · doi:10.1021/cr4006654 · Cited by 520
Ribonucleotide reductase and cancer: biological mechanisms and targeted therapies
Aye, Y., Li, M., Long, M. J. C., & Weiss, R. S. (2015) · Oncogene · doi:10.1038/onc.2014.155 · Cited by 436
One- and two-electron oxidation of thiols: mechanisms, kinetics and biological fates
Trujillo, M., Alvarez, B., & Radi, R. (2016) · Free Radical Research · doi:10.3109/10715762.2015.1089988 · Cited by 142
Detection of cell–cell interactions via photocatalytic cell tagging
Oslund, R. C., Reyes-Robles, T., White, C. H., Tomlinson, J. H., Crotty, K. A., Bowman, E. P., Chang, D., Peterson, V. M., Li, L., Frutos, S., et al. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01044-0 · Cited by 133
Houée-Lévin, C., Bobrowski, K., Horakova, L., Karademir, B., Schöneich, C., Davies, M. J., & Spickett, C. M. (2015) · Free Radical Research · doi:10.3109/10715762.2015.1007968 · Cited by 126
Metadata
- Authors
- Minnihan, E. C., Nocera, D. G., & Stubbe, J.
- Venue
- Accounts of Chemical Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2013-06-04
- Volume
- 46
- Issue
- 11
- Pages
- 2524-2535
- ISSN
- 0001-4842 (ISSN-L)
- 1520-4898
- OpenAlex
- W1981539002
- Cited by
- 269
- References
- 34
- FWCI
- 11.94
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
