The Phylogeny and Active Site Design of Eukaryotic Copper-only Superoxide Dismutases

Peterson, Ryan L.; Galaleldeen, Ahmad; Villarreal, Johanna; Taylor, Alexander B.; Cabelli, Diane E.; Hart, P. John; Culotta, Valeria C.

doi:10.1074/jbc.M116.748251

Title: The Phylogeny and Active Site Design of Eukaryotic Copper-only Superoxide Dismutases

Journal Article · Thu Sep 01 00:00:00 EDT 2016 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.M116.748251· OSTI ID:1769192

Peterson, Ryan L.; Galaleldeen, Ahmad; Villarreal, Johanna; Taylor, Alexander B.; Cabelli, Diane E.; Hart, P. John; Culotta, Valeria C.

In eukaryotes the bimetallic Cu/Zn superoxide dismutase (SOD) enzymes play important roles in the biology of reactive oxygen species by disproportionating superoxide anion. We reported that the fungal pathogen Candida albicans expresses a novel copper-only SOD, known as SOD5, that lacks the zinc cofactor and electrostatic loop (ESL) domain of Cu/Zn-SODs for substrate guidance. In spite of these abnormalities, C. albicans SOD5 can disproportionate superoxide at rates limited only by diffusion. Here we demonstrate that this curious copper-only SOD occurs throughout the fungal kingdom as well as in phylogenetically distant oomycetes or “pseudofungi” species. It is the only form of extracellular SOD in fungi and oomycetes, in stark contrast to the extracellular Cu/Zn-SODs of plants and animals. Through structural biology and biochemical approaches we demonstrate that these copper-only SODs have evolved with a specialized active site consisting of two highly conserved residues equivalent to SOD5 Glu-110 and Asp-113. The equivalent positions are zinc binding ligands in Cu/Zn-SODs and have evolved in copper-only SODs to control catalysis and copper binding in lieu of zinc and the ESL. Similar to the zinc ion in Cu/Zn-SODs, SOD5 Glu-110 helps orient a key copper-coordinating histidine and extends the pH range of enzyme catalysis. Furthermore, SOD5 Asp-113 connects to the active site in a manner similar to that of the ESL in Cu/Zn-SODs and assists in copper cofactor binding. Copper-only SODs are virulence factors for certain fungal pathogens; thus this unique active site may be a target for future anti-fungal strategies.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357; AC02-98-CH10886; SC00112704

OSTI ID:: 1769192

Alternate ID(s):: OSTI ID: 1336119

Report Number(s):: BNL-112573-2016-JA; S0021925820358725; PII: S0021925820358725

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Vol. 291 Journal Issue: 40; ISSN 0021-9258

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 22 works

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References (56)

Plant Parasitic Oomycetes Such as Phytophthora Species Contain Genes Derived from Three Eukaryotic Lineages Richards, Thomas A.; Talbot, Nicholas J. Plant Signaling & Behavior, Vol. 2, Issue 2 https://doi.org/10.4161/psb.2.2.3640	journal	March 2007
Adaptation to environmental pH in Candida albicans and its relation to pathogenesis Davis, Dana Current Genetics, Vol. 44, Issue 1 https://doi.org/10.1007/s00294-003-0415-2	journal	October 2003
A pH-dependent superoxide dismutase activity for zinc-free bovine erythrocuprein. Reexamination of the role of zinc in the holoprotein Pantoliano, M. Journal of Inorganic Biochemistry, Vol. 17, Issue 4 https://doi.org/10.1016/S0162-0134(00)80093-8	journal	January 1982
Binding of a Single Zinc Ion to One Subunit of Copper−Zinc Superoxide Dismutase Apoprotein Substantially Influences the Structure and Stability of the Entire Homodimeric Protein Potter, Soshanna Zittin; Zhu, Haining; Shaw, Bryan Francis Journal of the American Chemical Society, Vol. 129, Issue 15 https://doi.org/10.1021/ja066690+	journal	March 2007
Copper-Zinc Superoxide Dismutase and Amyotrophic Lateral Sclerosis Valentine, Joan Selverstone; Doucette, Peter A.; Zittin Potter, Soshanna Annual Review of Biochemistry, Vol. 74, Issue 1 https://doi.org/10.1146/annurev.biochem.72.121801.161647	journal	June 2005
The evolutionary phylogeny of the oomycete “fungi” Beakes, Gordon W.; Glockling, Sally L.; Sekimoto, Satoshi Protoplasma, Vol. 249, Issue 1 https://doi.org/10.1007/s00709-011-0269-2	journal	March 2011
Interplay between the Gastric Bacterial Microbiota and Candida albicans during Postantibiotic Recolonization and Gastritis Mason, Katie L.; Erb Downward, John R.; Falkowski, Nicole R. Infection and Immunity, Vol. 80, Issue 1 https://doi.org/10.1128/IAI.05162-11	journal	October 2011
pH-dependent migration of copper(II) to the vacant zinc-binding site of zinc-free bovine erythrocyte superoxide dismutase Valentine, J. S.; Pantoliano, M. W.; McDonnell, P. J. Proceedings of the National Academy of Sciences, Vol. 76, Issue 9 https://doi.org/10.1073/pnas.76.9.4245	journal	September 1979
Superoxide dismutase in extracellular fluids Marklund, Stefan L.; Holme, Elisabeth; Hellner, Louise Clinica Chimica Acta, Vol. 126, Issue 1 https://doi.org/10.1016/0009-8981(82)90360-6	journal	November 1982
Evolution of Filamentous Plant Pathogens: Gene Exchange across Eukaryotic Kingdoms Richards, Thomas A.; Dacks, Joel B.; Jenkinson, Joanna M. Current Biology, Vol. 16, Issue 18 https://doi.org/10.1016/j.cub.2006.07.052	journal	September 2006
Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. Crapo, J. D.; Oury, T.; Rabouille, C. Proceedings of the National Academy of Sciences, Vol. 89, Issue 21 https://doi.org/10.1073/pnas.89.21.10405	journal	November 1992
Essential role for the Menkes ATPase in activation of extracellular superoxide dismutase: implication for vascular oxidative stress Qin, Zhenyu; Itoh, Shinichi; Jeney, Viktoria The FASEB Journal, Vol. 20, Issue 2 https://doi.org/10.1096/fj.05-4564fje	journal	December 2005
SOD Enzymes and Microbial Pathogens: Surviving the Oxidative Storm of Infection Broxton, Chynna N.; Culotta, Valeria C. PLOS Pathogens, Vol. 12, Issue 1 https://doi.org/10.1371/journal.ppat.1005295	journal	January 2016
The Structure of Human Extracellular Copper–Zinc Superoxide Dismutase at 1.7 Å Resolution: Insights into Heparin and Collagen Binding Antonyuk, Svetlana V.; Strange, Richard W.; Marklund, Stefan L. Journal of Molecular Biology, Vol. 388, Issue 2 https://doi.org/10.1016/j.jmb.2009.03.026	journal	May 2009
The Fungal Pathogen Candida albicans Autoinduces Hyphal Morphogenesis by Raising Extracellular pH Vylkova, Slavena; Carman, Aaron J.; Danhof, Heather A. mBio, Vol. 2, Issue 3 https://doi.org/10.1128/mBio.00055-11	journal	May 2011
The role of arginine 143 in the electrostatics and mechanism of Cu, Zn superoxide dismutase: Computational and experimental evaluation by mutational analysis Fisher, Cindy L.; Cabelli, Diane E.; Tainer, John A. Proteins: Structure, Function, and Genetics, Vol. 19, Issue 1 https://doi.org/10.1002/prot.340190105	journal	May 1994
A Fraction of Yeast Cu,Zn-Superoxide Dismutase and Its Metallochaperone, CCS, Localize to the Intermembrane Space of Mitochondria Sturtz, Lori A.; Diekert, Kerstin; Jensen, Laran T. Journal of Biological Chemistry, Vol. 276, Issue 41 https://doi.org/10.1074/jbc.M105296200	journal	October 2001
Candida albicans SOD5 represents the prototype of an unprecedented class of Cu-only superoxide dismutases required for pathogen defense Gleason, J. E.; Galaleldeen, A.; Peterson, R. L. Proceedings of the National Academy of Sciences, Vol. 111, Issue 16 https://doi.org/10.1073/pnas.1400137111	journal	April 2014
Copper, Zinc Superoxide Dismutase in Escherichia coli: Periplasmic Localization Benov, L.; Chang, L. Y.; Day, B. Archives of Biochemistry and Biophysics, Vol. 319, Issue 2 https://doi.org/10.1006/abbi.1995.1324	journal	June 1995
Superoxide Dismutase McCord, Joe M.; Fridovich, Irwin Journal of Biological Chemistry, Vol. 244, Issue 22 https://doi.org/10.1016/S0021-9258(18)63504-5	journal	November 1969
Superoxide dismutase 1 (SOD1) is essential for H2O2-mediated oxidation and inactivation of phosphatases in growth factor signaling Juarez, J. C.; Manuia, M.; Burnett, M. E. Proceedings of the National Academy of Sciences, Vol. 105, Issue 20 https://doi.org/10.1073/pnas.0709451105	journal	May 2008
Reactions of Hydrogen Peroxide with Familial Amyotrophic Lateral Sclerosis Mutant Human Copper-Zinc Superoxide Dismutases Studied by Pulse Radiolysis Goto, Joy J.; Gralla, Edith Butler; Valentine, Joan Selverstone Journal of Biological Chemistry, Vol. 273, Issue 46 https://doi.org/10.1074/jbc.273.46.30104	journal	November 1998
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
SOD1 Integrates Signals from Oxygen and Glucose to Repress Respiration Reddi, Amit R.; Culotta, Valeria C. Cell, Vol. 152, Issue 1-2 https://doi.org/10.1016/j.cell.2012.11.046	journal	January 2013
Candida Infections of the Genitourinary Tract Achkar, Jacqueline M.; Fries, Bettina C. Clinical Microbiology Reviews, Vol. 23, Issue 2 https://doi.org/10.1128/CMR.00076-09	journal	April 2010
Glycosylation of extracellular superoxide dismutase studied by high-performance liquid chromatography and mass spectrometry Strömqvist, Mats; Holgersson, Jan; Samuelsson, Bo Journal of Chromatography A, Vol. 548 https://doi.org/10.1016/S0021-9673(01)88611-8	journal	July 1991
Unusual Trigonal-Planar Copper Configuration Revealed in the Atomic Structure of Yeast Copper−Zinc Superoxide Dismutase ^† ^, ^‡ Ogihara, Nancy L.; Parge, Hans E.; Hart, P. John Biochemistry, Vol. 35, Issue 7 https://doi.org/10.1021/bi951930b	journal	January 1996
Unique Features of the sodC -encoded Superoxide Dismutase from Mycobacterium tuberculosis , a Fully Functional Copper-containing Enzyme Lacking Zinc in the Active Site Spagnolo, Laura; Törö, Imre; D'Orazio, Melania Journal of Biological Chemistry, Vol. 279, Issue 32 https://doi.org/10.1074/jbc.M404699200	journal	May 2004
Horizontal gene transfer facilitated the evolution of plant parasitic mechanisms in the oomycetes Richards, T. A.; Soanes, D. M.; Jones, M. D. M. Proceedings of the National Academy of Sciences, Vol. 108, Issue 37 https://doi.org/10.1073/pnas.1105100108	journal	August 2011
Loss of in Vitro Metal Ion Binding Specificity in Mutant Copper-Zinc Superoxide Dismutases Associated with Familial Amyotrophic Lateral Sclerosis Goto, J. J.; Zhu, H.; Sanchez, R. J. Journal of Biological Chemistry, Vol. 275, Issue 2 https://doi.org/10.1074/jbc.275.2.1007	journal	January 2000
Extracellular Superoxide Dismutase Protects Histoplasma Yeast Cells from Host-Derived Oxidative Stress Youseff, Brian H.; Holbrook, Eric D.; Smolnycki, Katherine A. PLoS Pathogens, Vol. 8, Issue 5 https://doi.org/10.1371/journal.ppat.1002713	journal	May 2012
Superoxide Radical and Superoxide Dismutases Fridovich, Irwin Annual Review of Biochemistry, Vol. 64, Issue 1 https://doi.org/10.1146/annurev.bi.64.070195.000525	journal	June 1995
Computational, pulse-radiolytic, and structural investigations of lysine-136 and its role in the electrostatic triad of human C u,Z n superoxide dismutase Fisher, Cindy L.; Cabelli, Diane E.; Hallewell, Robert A. Proteins: Structure, Function, and Genetics, Vol. 29, Issue 1 https://doi.org/10.1002/(SICI)1097-0134(199709)29:1<103::AID-PROT8>3.0.CO;2-G	journal	September 1997
Dynamics and Innovations within Oomycete Genomes: Insights into Biology, Pathology, and Evolution Judelson, Howard S. Eukaryotic Cell, Vol. 11, Issue 11 https://doi.org/10.1128/EC.00155-12	journal	August 2012
Cellular Responses of Candida albicans to Phagocytosis and the Extracellular Activities of Neutrophils Are Critical to Counteract Carbohydrate Starvation, Oxidative and Nitrosative Stress Miramón, Pedro; Dunker, Christine; Windecker, Hanna PLoS ONE, Vol. 7, Issue 12 https://doi.org/10.1371/journal.pone.0052850	journal	December 2012
State of play in amyotrophic lateral sclerosis genetics Renton, Alan E.; Chiò, Adriano; Traynor, Bryan J. Nature Neuroscience, Vol. 17, Issue 1 https://doi.org/10.1038/nn.3584	journal	December 2013
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Copper−Zinc Superoxide Dismutase: Why Not pH-Dependent? Ellerby, Lisa M.; Cabelli, Diane E.; Graden, Janet A. Journal of the American Chemical Society, Vol. 118, Issue 28 https://doi.org/10.1021/ja953845x	journal	January 1996
Disrupted Zinc-Binding Sites in Structures of Pathogenic SOD1 Variants D124V and H80R Seetharaman, Sai V.; Winkler, Duane D.; Taylor, Alexander B. Biochemistry, Vol. 49, Issue 27 https://doi.org/10.1021/bi100314n	journal	July 2010
Decreased Metallation and Activity in Subsets of Mutant Superoxide Dismutases Associated with Familial Amyotrophic Lateral Sclerosis Hayward, Lawrence J.; Rodriguez, Jorge A.; Kim, Ji W. Journal of Biological Chemistry, Vol. 277, Issue 18 https://doi.org/10.1074/jbc.M112087200	journal	February 2002
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Faster superoxide dismutase mutants designed by enhancing electrostatic guidance Getzoff, Elizabeth D.; Cabelli, Diane E.; Fisher, Cindy L. Nature, Vol. 358, Issue 6384 https://doi.org/10.1038/358347a0	journal	July 1992
Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles' heel? Sabharwal, Simran S.; Schumacker, Paul T. Nature Reviews Cancer, Vol. 14, Issue 11 https://doi.org/10.1038/nrc3803	journal	October 2014
Superoxide Dismutases: Role in Redox Signaling, Vascular Function, and Diseases Fukai, Tohru; Ushio-Fukai, Masuko Antioxidants & Redox Signaling, Vol. 15, Issue 6 https://doi.org/10.1089/ars.2011.3999	journal	September 2011
A characterization of copper/zinc superoxide dismutase mutants at position 124 Zinc-deficient proteins Banci, Lucia; Bertini, Ivano; Cabelli, Diane E. European Journal of Biochemistry, Vol. 196, Issue 1 https://doi.org/10.1111/j.1432-1033.1991.tb15794.x	journal	February 1991
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis Rosen, Daniel R.; Siddique, Teepu; Patterson, David Nature, Vol. 362, Issue 6415 https://doi.org/10.1038/362059a0	journal	March 1993
Oomycetes and fungi: similar weaponry to attack plants Latijnhouwers, Maita; de Wit, Pierre J. G. M.; Govers, Francine Trends in Microbiology, Vol. 11, Issue 10 https://doi.org/10.1016/j.tim.2003.08.002	journal	October 2003
Superoxide dismutase: A comparison of rate constants Forman, Henry J.; Fridovich, Irwin Archives of Biochemistry and Biophysics, Vol. 158, Issue 1 https://doi.org/10.1016/0003-9861(73)90636-X	journal	September 1973
Copper- and zinc-containing superoxide dismutase (Cu/ZnSOD) is required for the protection of Candida albicans against oxidative stresses and the expression of its full virulence Hwang, Cheol-Sang; Rhie, Gi-eun; Oh, Jang-Hyun Microbiology, Vol. 148, Issue 11 https://doi.org/10.1099/00221287-148-11-3705	journal	November 2002
Superoxide Dismutases and Superoxide Reductases Sheng, Yuewei; Abreu, Isabel A.; Cabelli, Diane E. Chemical Reviews, Vol. 114, Issue 7 https://doi.org/10.1021/cr4005296	journal	January 2014
The structural biochemistry of the superoxide dismutases Perry, J. J. P.; Shin, D. S.; Getzoff, E. D. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1804, Issue 2 https://doi.org/10.1016/j.bbapap.2009.11.004	journal	February 2010
Superoxide dismutases—a review of the metal-associated mechanistic variations Abreu, Isabel A.; Cabelli, Diane E. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1804, Issue 2 https://doi.org/10.1016/j.bbapap.2009.11.005	journal	February 2010
A Structure-Based Mechanism for Copper−Zinc Superoxide Dismutase ^† ^, ^‡ Hart, P. John; Balbirnie, Melinda M.; Ogihara, Nancy L. Biochemistry, Vol. 38, Issue 7 https://doi.org/10.1021/bi982284u	journal	February 1999
Adaptations of Candida albicans for Growth in the Mammalian Intestinal Tract Rosenbach, Ari; Dignard, Daniel; Pierce, Jessica V. Eukaryotic Cell, Vol. 9, Issue 7 https://doi.org/10.1128/EC.00034-10	journal	April 2010
Superoxide dismutase as a target for the selective killing of cancer cells Huang, Peng; Feng, Li; Oldham, Elizabeth A. Nature, Vol. 407, Issue 6802 https://doi.org/10.1038/35030140	journal	September 2000
Human copper-containing superoxide dismutase of high molecular weight. Marklund, S. L. Proceedings of the National Academy of Sciences, Vol. 79, Issue 24 https://doi.org/10.1073/pnas.79.24.7634	journal	December 1982

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
copper
enzyme
fungi
superoxide dismutase (SOD)
superoxide ion
x-ray crystallography

Title: The Phylogeny and Active Site Design of Eukaryotic Copper-only Superoxide Dismutases

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Cited By (2)

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