Structural and biochemical analyses indicate that a bacterial persulfide dioxygenase–rhodanese fusion protein functions in sulfur assimilation

Motl, Nicole; Skiba, Meredith A.; Kabil, Omer; Smith, Janet L.; Banerjee, Ruma

doi:10.1074/jbc.m117.790170

Structural and biochemical analyses indicate that a bacterial persulfide dioxygenase–rhodanese fusion protein functions in sulfur assimilation

Journal Article · Thu Jul 06 00:00:00 EDT 2017 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.m117.790170· OSTI ID:1397309

Motl, Nicole ^[1]; Skiba, Meredith A. ^[2]; Kabil, Omer ^[1]; Smith, Janet L. ^[2]; Banerjee, Ruma ^[1]

Univ. of Michigan Medical Center, Ann Arbor, MI (United States). Dept. of Biological Chemistry
Univ. of Michigan Medical Center, Ann Arbor, MI (United States). Dept. of Biological Chemistry; Univ. of Michigan, Ann Arbor, MI (United States). Life Sciences Inst.

Hydrogen sulfide (H₂S) is a signaling molecule that is toxic at elevated concentrations. In eukaryotes, it is cleared via a mitochondrial sulfide oxidation pathway, which comprises sulfide quinone oxidoreductase, persulfide dioxygenase (PDO), rhodanese, and sulfite oxidase and converts H₂S to thiosulfate and sulfate. Natural fusions between the non-heme iron containing PDO and rhodanese, a thiol sulfurtransferase, exist in some bacteria. However, little is known about the role of the PDO–rhodanese fusion (PRF) proteins in sulfur metabolism. Herein, we report the kinetic properties and the crystal structure of a PRF from the Gram-negative endophytic bacterium Burkholderia phytofirmans. The crystal structures of wild-type PRF and a sulfurtransferase-inactivated C314S mutant with and without glutathione were determined at 1.8, 2.4, and 2.7 Å resolution, respectively. We found that the two active sites are distant and do not show evidence of direct communication. The B. phytofirmans PRF exhibited robust PDO activity and preferentially catalyzed sulfur transfer in the direction of thiosulfate to sulfite and glutathione persulfide; sulfur transfer in the reverse direction was detectable only under limited turnover conditions. Together with the kinetic data, our bioinformatics analysis reveals that B. phytofirmans PRF is poised to metabolize thiosulfate to sulfite in a sulfur assimilation pathway rather than in sulfide stress response as seen, for example, with the Staphylococcus aureus PRF or sulfide oxidation and disposal as observed with the homologous mammalian proteins.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC)

OSTI ID:: 1397309

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 34 Vol. 292; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (51)

Enzyme activity as an indicator of red cell age Sass, Martin D.; Vorsanger, Eric; Spear, Paul W. Clinica Chimica Acta, Vol. 10, Issue 1 https://doi.org/10.1016/0009-8981(64)90210-4	journal	July 1964
Thiosulfate reductase Chauncey, Thomas R.; Uhteg, Lawrence C.; Westley, John Methods in Enzymology https://doi.org/10.1016/0076-6879(87)43062-0	book	January 1987
PLP-dependent H2S biogenesis Singh, Sangita; Banerjee, Ruma Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1814, Issue 11 https://doi.org/10.1016/j.bbapap.2011.02.004	journal	November 2011
H2S and its role in redox signaling Kabil, Omer; Motl, Nicole; Banerjee, Ruma Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1844, Issue 8 https://doi.org/10.1016/j.bbapap.2014.01.002	journal	August 2014
Catalytic promiscuity and heme-dependent redox regulation of H 2 S synthesis Banerjee, Ruma Current Opinion in Chemical Biology, Vol. 37 https://doi.org/10.1016/j.cbpa.2017.02.021	journal	April 2017
The “Rhodanese” Fold and Catalytic Mechanism of 3-Mercaptopyruvate Sulfurtransferases: Crystal Structure of SseA from Escherichia coli Spallarossa, Andrea; Forlani, Fabio; Carpen, Aristodemo Journal of Molecular Biology, Vol. 335, Issue 2 https://doi.org/10.1016/j.jmb.2003.10.072	journal	January 2004
Conformational Analysis and Chemical Reactivity of the Multidomain Sulfurtransferase, Staphylococcus aureus CstA Higgins, Khadine A.; Peng, Hui; Luebke, Justin L. Biochemistry, Vol. 54, Issue 14 https://doi.org/10.1021/acs.biochem.5b00056	journal	April 2015
Staphylococcus aureus CstB Is a Novel Multidomain Persulfide Dioxygenase-Sulfurtransferase Involved in Hydrogen Sulfide Detoxification Shen, Jiangchuan; Keithly, Mary E.; Armstrong, Richard N. Biochemistry, Vol. 54, Issue 29 https://doi.org/10.1021/acs.biochem.5b00584	journal	July 2015
Staphylococcus aureus sqr Encodes a Type II Sulfide:Quinone Oxidoreductase and Impacts Reactive Sulfur Speciation in Cells Shen, Jiangchuan; Peng, Hui; Zhang, Yixiang Biochemistry, Vol. 55, Issue 47 https://doi.org/10.1021/acs.biochem.6b00714	journal	November 2016
Human liver rhodanese. Nonlinear kinetic behavior in a double displacement mechanism Jarabak, Rebecca; Westley, John Biochemistry, Vol. 13, Issue 16 https://doi.org/10.1021/bi00713a006	journal	July 1974
Biosynthesis of a Central Intermediate in Hydrogen Sulfide Metabolism by a Novel Human Sulfurtransferase and Its Yeast Ortholog Melideo, Scott L.; Jackson, Michael R.; Jorns, Marilyn Schuman Biochemistry, Vol. 53, Issue 28 https://doi.org/10.1021/bi500650h	journal	July 2014
Biosynthesis and Reactivity of Cysteine Persulfides in Signaling Yadav, Pramod K.; Martinov, Michael; Vitvitsky, Victor Journal of the American Chemical Society, Vol. 138, Issue 1 https://doi.org/10.1021/jacs.5b10494	journal	December 2015
The covalent and tertiary structure of bovine liver rhodanese Ploegman, Jan H.; Drent, Gé; Kalk, Kor H. Nature, Vol. 273, Issue 5658 https://doi.org/10.1038/273124a0	journal	May 1978
Identification and characterization of a bacterial hydrosulphide ion channel Czyzewski, Bryan K.; Wang, Da-Neng Nature, Vol. 483, Issue 7390 https://doi.org/10.1038/nature10881	journal	March 2012
Biogenesis of reactive sulfur species for signaling by hydrogen sulfide oxidation pathways Mishanina, Tatiana V.; Libiad, Marouane; Banerjee, Ruma Nature Chemical Biology, Vol. 11, Issue 7 https://doi.org/10.1038/nchembio.1834	journal	June 2015
Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy Tiranti, Valeria; Viscomi, Carlo; Hildebrandt, Tatjana Nature Medicine, Vol. 15, Issue 2 https://doi.org/10.1038/nm.1907	journal	January 2009
Endogenous and Exogenous Hydrogen Sulfide Promotes Resolution of Colitis in Rats Wallace, John L.; Vong, Linda; McKnight, Webb Gastroenterology, Vol. 137, Issue 2 https://doi.org/10.1053/j.gastro.2009.04.012	journal	August 2009
Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function Elrod, J. W.; Calvert, J. W.; Morrison, J. Proceedings of the National Academy of Sciences, Vol. 104, Issue 39 https://doi.org/10.1073/pnas.0705891104	journal	September 2007
Electrostatics of nanosystems: Application to microtubules and the ribosome Baker, N. A.; Sept, D.; Joseph, S. Proceedings of the National Academy of Sciences, Vol. 98, Issue 18, p. 10037-10041 https://doi.org/10.1073/pnas.181342398	journal	August 2001
Characterization of Patient Mutations in Human Persulfide Dioxygenase (ETHE1) Involved in H2S Catabolism Kabil, Omer; Banerjee, Ruma Journal of Biological Chemistry, Vol. 287, Issue 53 https://doi.org/10.1074/jbc.M112.407411	journal	December 2012
Organization of the Human Mitochondrial Hydrogen Sulfide Oxidation Pathway Libiad, Marouane; Yadav, Pramod Kumar; Vitvitsky, Victor Journal of Biological Chemistry, Vol. 289, Issue 45 https://doi.org/10.1074/jbc.M114.602664	journal	September 2014
Characterizations of Two Bacterial Persulfide Dioxygenases of the Metallo-β-lactamase Superfamily Sattler, Steven A.; Wang, Xia; Lewis, Kevin M. Journal of Biological Chemistry, Vol. 290, Issue 31 https://doi.org/10.1074/jbc.M115.652537	journal	July 2015
Polymorphic Variants of Human Rhodanese Exhibit Differences in Thermal Stability and Sulfur Transfer Kinetics Libiad, Marouane; Sriraman, Anusha; Banerjee, Ruma Journal of Biological Chemistry, Vol. 290, Issue 39 https://doi.org/10.1074/jbc.M115.675694	journal	August 2015
Redox Biochemistry of Hydrogen Sulfide Kabil, Omer; Banerjee, Ruma Journal of Biological Chemistry, Vol. 285, Issue 29 https://doi.org/10.1074/jbc.R110.128363	journal	May 2010
Ethylmalonic Encephalopathy Is Caused by Mutations in ETHE1, a Gene Encoding a Mitochondrial Matrix Protein Tiranti, Valeria; D’Adamo, Pio; Briem, Egill The American Journal of Human Genetics, Vol. 74, Issue 2 https://doi.org/10.1086/381653	journal	February 2004
Hydrogen Sulfide: From Brain to Gut Kimura, Hideo Antioxidants & Redox Signaling, Vol. 12, Issue 9 https://doi.org/10.1089/ars.2009.2919	journal	May 2010
High Turnover Rates for Hydrogen Sulfide Allow for Rapid Regulation of Its Tissue Concentrations Vitvitsky, Victor; Kabil, Omer; Banerjee, Ruma Antioxidants & Redox Signaling, Vol. 17, Issue 1 https://doi.org/10.1089/ars.2011.4310	journal	July 2012
FIMO: scanning for occurrences of a given motif Grant, Charles E.; Bailey, Timothy L.; Noble, William Stafford Bioinformatics, Vol. 27, Issue 7 https://doi.org/10.1093/bioinformatics/btr064	journal	February 2011
A Simple Serum Iron Method Using the New Sensitive Chromogen Tripyridyl-s-triazine Fischer, David S.; Price, David C. Clinical Chemistry, Vol. 10, Issue 1 https://doi.org/10.1093/clinchem/10.1.21	journal	January 1964
The rhodanese/Cdc25 phosphatase superfamily: Sequence-structure-function relations Bordo, D. EMBO Reports, Vol. 3, Issue 8 https://doi.org/10.1093/embo-reports/kvf150	journal	August 2002
The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener Zhao, W. The EMBO Journal, Vol. 20, Issue 21 https://doi.org/10.1093/emboj/20.21.6008	journal	November 2001
Crystal structure of human persulfide dioxygenase: structural basis of ethylmalonic encephalopathy Pettinati, I.; Brem, J.; McDonough, M. A. Human Molecular Genetics, Vol. 24, Issue 9 https://doi.org/10.1093/hmg/ddv007	journal	January 2015
PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations Dolinsky, T. J.; Nielsen, J. E.; McCammon, J. A. Nucleic Acids Research, Vol. 32, Issue Web Server, p. W665-W667 https://doi.org/10.1093/nar/gkh381	journal	July 2004
PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations Dolinsky, T. J.; Czodrowski, P.; Li, H. Nucleic Acids Research, Vol. 35, Issue Web Server https://doi.org/10.1093/nar/gkm276	journal	May 2007
Burkholderia phytofirmans sp. nov., a novel plant-associated bacterium with plant-beneficial properties Sessitsch, A. INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, Vol. 55, Issue 3 https://doi.org/10.1099/ijs.0.63149-0	journal	May 2005
Structure and function of the LysR-type transcriptional regulator (LTTR) family proteins Maddocks, S. E.; Oyston, P. C. F. Microbiology, Vol. 154, Issue 12 https://doi.org/10.1099/mic.0.2008/022772-0	journal	December 2008
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Structure of an ETHE1-like protein from Arabidopsis thaliana McCoy, Jason G.; Bingman, Craig A.; Bitto, Eduard Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 9 https://doi.org/10.1107/S0907444906020592	journal	August 2006
BALBES : a molecular-replacement pipeline Long, Fei; Vagin, Alexei A.; Young, Paul Acta Crystallographica Section D Biological Crystallography, Vol. 64, Issue 1 https://doi.org/10.1107/S0907444907050172	journal	December 2007
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
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
Three enzymatic activities catalyze the oxidation of sulfide to thiosulfate in mammalian and invertebrate mitochondria: Reactions of mitochondrial sulfide oxidation Hildebrandt, Tatjana M.; Grieshaber, Manfred K. FEBS Journal, Vol. 275, Issue 13 https://doi.org/10.1111/j.1742-4658.2008.06482.x	journal	June 2008
The CsoR ‐like sulfurtransferase repressor ( CstR ) is a persulfide sensor in S taphylococcus aureus Luebke, Justin L.; Shen, Jiangchuan; Bruce, Kevin E. Molecular Microbiology, Vol. 94, Issue 6 https://doi.org/10.1111/mmi.12835	journal	November 2014
H2S: A Universal Defense Against Antibiotics in Bacteria Shatalin, K.; Shatalina, E.; Mironov, A. Science, Vol. 334, Issue 6058 https://doi.org/10.1126/science.1209855	journal	November 2011
Regulation of Sulfur Assimilation Pathways in Burkholderia cenocepacia through Control of Genes by the SsuR Transcription Factor Lochowska, A.; Iwanicka-Nowicka, R.; Zielak, A. Journal of Bacteriology, Vol. 193, Issue 8 https://doi.org/10.1128/JB.00483-10	journal	February 2011
Regulation of Sulfur Assimilation Pathways in Burkholderia cenocepacia: Identification of Transcription Factors CysB and SsuR and Their Role in Control of Target Genes Iwanicka-Nowicka, R.; Zielak, A.; Cook, A. M. Journal of Bacteriology, Vol. 189, Issue 5 https://doi.org/10.1128/JB.00592-06	journal	September 2006
ETHE1 mutations are specific to ethylmalonic encephalopathy Tiranti, V. Journal of Medical Genetics, Vol. 43, Issue 4 https://doi.org/10.1136/jmg.2005.036210	journal	September 2005
A Critical Review of the Literature on Hydrogen Sulfide Toxicity Beauchamp, R. O.; Bus, James S.; Popp, James A. CRC Critical Reviews in Toxicology, Vol. 13, Issue 1 https://doi.org/10.3109/10408448409029321	journal	January 1984
Crystalline Rhodanese. II. The Enzyme Catalyzed Reaction. Sörbo, Bo H.; Lagerkvist, Ulf; Pesola, Rainer Acta Chemica Scandinavica, Vol. 7 https://doi.org/10.3891/acta.chem.scand.07-1137	journal	January 1953
Quantitative H2S-mediated protein sulfhydration reveals metabolic reprogramming during the integrated stress response Gao, Xing-Huang; Krokowski, Dawid; Guan, Bo-Jhih eLife, Vol. 4 https://doi.org/10.7554/eLife.10067	journal	November 2015

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Cerebellar dyssynergia in humans?A quantitative analysis Miller, Robert G.; Freund, Hans-J. Annals of Neurology, Vol. 8, Issue 6 https://doi.org/10.1002/ana.410080605	journal	December 1980
Mechanism-based inhibition of human persulfide dioxygenase by γ-glutamyl-homocysteinyl-glycine Kabil, Omer; Motl, Nicole; Strack, Martin Journal of Biological Chemistry, Vol. 293, Issue 32 https://doi.org/10.1074/jbc.ra118.004096	journal	July 2018
Rhodanese domain-containing sulfurtransferases: multifaceted proteins involved in sulfur trafficking in plants Selles, Benjamin; Moseler, Anna; Rouhier, Nicolas Journal of Experimental Botany, Vol. 70, Issue 16 https://doi.org/10.1093/jxb/erz213	journal	May 2019
The Complete Pathway for Thiosulfate Utilization in Saccharomyces cerevisiae Chen, Zhigang; Zhang, Xi; Li, Huanjie Applied and Environmental Microbiology, Vol. 84, Issue 22 https://doi.org/10.1128/aem.01241-18	journal	November 2018

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X-ray crystallography
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hydrogen sulfide
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Structural and biochemical analyses indicate that a bacterial persulfide dioxygenase–rhodanese fusion protein functions in sulfur assimilation

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