Electrostatic recognition between superoxide and copper, zinc superoxide dismutase
Abstract
Electrostatic forces have been implicated in a variety of biologically important molecular interactions including drug orientation by DNA, protein folding and assembly, substrate binding and catalysis and macromolecular complementarity with inhibitors, drugs and hormones. To examine enzyme-substrate interactions in copper, zinc superoxide dismutase (SOD), we developed a method for the visualization and analysis of an enzyme's three-dimensional electrostatic vector field that allows the contributions of specific residues to be identified. We report here that the arrangement of electrostatic charges in SOD promotes productive enzyme-substrate interaction through substrate guidance and charge complementarity: sequence-conserved residues create an extensive electrostatic field that directs the negatively charged superoxide (O-2) substrate to the highly positive catalytic binding site at the bottom of the active-site channel. Dissection of the electrostatic potential gradient indicated the relative contributions of individual charged residues: Lys 134 and Glu 131 seem to have important roles in directing the long-range approach of O-2, while Arg 141 has local orienting effects. The reported methods of analysis may have general application for the elucidation of intermolecular recognition processes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several studies have been carried out using pulsed radiolysis to generate HO2•/O2•− and to understand the Cu,Zn-SOD-catalysed reaction of superoxide dismutation.
“Several studies have been carried out using pulsed radiolysis to generate HO2•/O2•− and to understand the Cu,Zn-SOD-catalysed reaction of superoxide dismutation [74,75,76,77], Figure 32.”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [76]
Cites
Warshel, A., & Levitt, M. (1976) · Journal of Molecular Biology · doi:10.1016/0022-2836(76)90311-9 · Cited by 3,821 · see citing works
Solvent-Accessible Surfaces of Proteins and Nucleic Acids
Connolly, M. L. (1983) · Science · doi:10.1126/science.6879170 · Cited by 2,759 · see citing works
Weiner, P. K., & Kollman, P. A. (1981) · Journal of Computational Chemistry · doi:10.1002/jcc.540020311 · Cited by 1,192 · see citing works
Self-citationElectrostatic Effects in Proteins
Perutz, M. F. (1978) · Science · doi:10.1126/science.694508 · Cited by 749 · see citing works
Oxygen and oxy‐radicals in chemistry and biology
Halliwell, B. B. (1982) · FEBS Letters · doi:10.1016/0014-5793(82)80255-x · Cited by 554 · see citing works
Klug-Roth, D., Rabani, J., & Fridovich, I. (1972) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)44987-9 · Cited by 495 · see citing works
Electrostatic potential molecular surfaces.
Weiner, P. K., Langridge, R., Blaney, J. M., et al. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.12.3754 · Cited by 448 · see citing works
Self-citationConformational Properties of Macromolecules
(1973) · Elsevier eBooks · doi:10.1016/b978-0-12-355550-2.x5001-7 · Cited by 309 · see citing works
Side-chain torsional potentials: effect of dipeptide, protein, and solvent environment
Gelin, B. R., & Karplus, M. (1979) · Biochemistry · doi:10.1021/bi00574a022 · Cited by 292 · see citing works
Dipoles of the α-helix and β-sheet: their role in protein folding
Hol, W. G. J., Halie, L., & Sander, C. (1981) · Nature · doi:10.1038/294532a0 · Cited by 276 · see citing works
Conformational properties of macromolecules
Gordon, M. (1974) · Polymer · doi:10.1016/0032-3861(74)90167-0 · Cited by 218 · see citing works
Electrostatic interactions in the reaction mechanism of bovine erythrocyte superoxide dismutase
Cudd, A., & Fridovich, I. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)33779-7 · Cited by 211 · see citing works
Oxygen and oxy-radicals in chemistry and biology
Rodgers, M. A. J., & Powers, E. L. (1981) · Academic Press eBooks · Cited by 202 · see citing works
Computer simulation of ionic systems: The distorting effects of the boundary conditions
Adams, D. J. (1979) · Chemical Physics Letters · doi:10.1016/0009-2614(79)80190-6 · Cited by 153 · see citing works
alpha-Helix dipole model and electrostatic stabilization of 4-alpha-helical proteins.
Sheridan, R. P., Levy, R. M., & Salemme, F. R. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.15.4545 · Cited by 132 · see citing works
Blaney, J. M., Weiner, P. K., Dearing, A., et al. (1982) · Journal of the American Chemical Society · doi:10.1021/ja00387a046 · Cited by 128 · see citing works
Self-citationO'Donnell, T. J., & Olson, A. J. (1981) · ACM SIGGRAPH Computer Graphics · doi:10.1145/965161.806799 · Cited by 72 · see citing works
Hayes, D. M., & Kollman, P. A. (1976) · Journal of the American Chemical Society · doi:10.1021/ja00440a057 · Cited by 67 · see citing works
Self-citationThe active site electrostatic potential of human carbonic anhydrase
Sheridan, R. P., & Allen, L. C. (1981) · Journal of the American Chemical Society · doi:10.1021/ja00396a042 · Cited by 66 · see citing works
O'Donnell, T. J., & Olson, A. J. (1981) · ACM SIGGRAPH Annual Conference on Computer Graphics and Interactive Techniques (SIGGRAPH) · doi:10.1145/800224.806799 · Cited by 62 · see citing works
Two Aspects of DNA Polymorphism and Microheterogeneity:
Pullman, B., Lavery, R., & Pullman, A. (1982) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1982.tb06582.x · Cited by 59 · see citing works
Molecular mechanical studies of proflavine and acridine orange intercalation
Dearing, A., Weiner, P. K., & Kollman, P. A. (1981) · Nucleic Acids Research · doi:10.1093/nar/9.6.1483 · Cited by 36 · see citing works
Self-citationSalin, M. L., & Wilson, W. W. (1981) · Molecular and Cellular Biochemistry · doi:10.1007/bf02357032 · Cited by 36 · see citing works
Brothers, P. J., & Ghosh, A. (2022) · doi:10.1002/9781119129301.ch4 · Cited by 31 · see citing works
Friend, S. H., March, K. L., Hanania, G. I. H., et al. (1980) · Biochemistry · doi:10.1021/bi00554a032 · Cited by 26 · see citing works
DRUG‐RECEPTOR RECOGNITION: ELECTROSTATIC FIELD LINES AT THE RECEPTOR AND DIELECTRIC EFFECTS
Dean, P. M. (1981) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1981.tb09953.x · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
[1] Role of free radicals and catalytic metal ions in human disease: An overview
Halliwell, B., & Gutteridge, J. M. C. (1990) · Methods in Enzymology · doi:10.1016/0076-6879(90)86093-b · Cited by 4,994 · see citing works
Oxygen free radicals and iron in relation to biology and medicine: Some problems and concepts
Halliwell, B., & Gutteridge, J. M. C. (1986) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(86)90305-x · Cited by 2,038 · see citing works
The importance of free radicals and catalytic metal ions in human diseases.
Halliwell, B., & Gutteridge, J. M. C. (1985) · Molecular Aspects of Medicine · doi:10.1016/0098-2997(85)90001-9 · Cited by 941 · see citing works
Superoxide dismutases—A review of the metal-associated mechanistic variations
Abreu, I. A., & Cabelli, D. E. (2010) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.11.005 · Cited by 563 · see citing works
Faster superoxide dismutase mutants designed by enhancing electrostatic guidance
Getzoff, E. D., Cabelli, D. E., Fisher, C. L., Parge, H. E., Viezzoli, M. S., Banci, L., & Hallewell, R. A. (1992) · Nature · doi:10.1038/358347a0 · Cited by 399 · see citing works
Self-citationSuperoxide Anion Chemistry—Its Role at the Core of the Innate Immunity
Andrés, C. M. C., Pérez de la Lastra, J. M., Andrés Juan, C., Plou, F. J., & Pérez-Lebeña, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031841 · Cited by 342 · see citing works
Copper–zinc superoxide dismutase: Why not pH-dependent?
Ellerby, L. M., Cabelli, D. E., Graden, J. A., & Valentine, J. S. (1996) · Journal of the American Chemical Society · doi:10.1021/ja953845x · Cited by 184 · see citing works
Fuss, J. O., & Tainer, J. A. (2011) · DNA Repair · doi:10.1016/j.dnarep.2011.04.028 · Cited by 170 · see citing works
Self-citationFisher, C. L., Cabelli, D. E., Tainer, J. A., Hallewell, R. A., & Getzoff, E. D. (1994) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.340190105 · Cited by 125 · see citing works
Self-citationStructure of fully reduced bovine copper zinc superoxide dismutase at 1.15 Å
Hough, M. A., & Hasnain, S. S. (2003) · Structure · doi:10.1016/s0969-2126(03)00155-2 · Cited by 80 · see citing works
- Authors
- Getzoff, E. D., Tainer, J. A., Weiner, P. K., Kollman, P. A., Richardson, J. S., & Richardson, D. C.
- Affiliations
- Scripps Research Institute (US)
- University of California, San Francisco (US)
- Duke University (US)
- Venue
- Nature
- Published
- 1983-11
- Volume
- 306
- Issue
- 5940
- Pages
- 287-290
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1969941075
- Cited by
- 554
- References
- 26
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 8 · 2023: 10 · 2022: 4 · 2021: 6 · 2020: 15 · 2019: 10 · 2018: 13 · 2017: 15 · 2016: 8 · 2015: 7 · 2014: 8 · 2013: 8 · 2012: 7
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- copper-zinc superoxide dismutase, superoxide, electrostatic potential, substrate binding, substrate recognition, charge complementarity, charged residues
- MeSH terms
- Binding Sites, Copper, Electricity, Hydrogen-Ion Concentration, Ions, Models, Molecular, Protein Conformation, Superoxide Dismutase, Zinc
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
