Dokument
Dokument

Summary:
Copper is an essential cofactor for many enzymes and over a threshold, it is toxic for all organisms. The redox ability of copper to cycle between two oxidation states, Cu(I) and Cu(II) makes it crucial for the structure and function numerous enzymes. Uncontrolled accumulation of copper inside the cell leads to the generation of reactive oxygen species (ROS) through fenton reaction leading to oxidative stress and finally damages DNA and proteins. In this work, the gram positive bacterium Bacillus subtilis was used to understand the mechanisms underlying copper homeostasis. Especially, the recently identified copper efflux transcriptional regulator CsoR was mainly in focus. Deletion mutant of ΔcsoR shows a growth defective phenotype in copper excess conditions and exhibited a slight better growth phenotype under copper limiting conditions. Microarray studies initiated with ΔcsoR under copper limiting conditions revealed the ycnJ gene to encode a protein that plays an important role in copper metabolism, as it shows a significant 8-fold upregulation under copper limiting conditions, and its disruption exhibits a growth defective phenotype under copper limiting as well as copper excess conditions. Native gel shift experiments with the recombinant Nterminal cytosolic domain of the YcnJ membrane protein (135 residues) disclose its strong affinity to Cu(II) atoms in vitro. Inspection of the upstream sequence of ycnJ revealed the ycnK gene to encode a putative transcriptional regulator, whose deletion showed a constitutive expression of ycnJ. Further studies supported a predominant role for the YcnJ protein not only as a copper importer under copper limiting conditions, but also possibly as a copper resistance determinant under copper excess conditions. Interestingly, the correlation between copper dependent iron aquisition was also elucidiated. Microarray approach to identify the copper responsive genes using ΔcsoR mutant exhibited an alternate regulation of iron responsive genes in the presence or absence of copper. Significant downregulation of the following iron responsive genes was observed: 1. dhbABCEF which is involved in bacillibactin production, 2. feuABC which are responsible for bacillibactin uptake and 3. besA and btr, which are involved in sensing iron bound bacilibactin, hydrolysis, cleavage and subsequent release of iron from bacillibactin. Transcription profiling data, quantification of bacillibactin amounts and estimation of total cellular iron and copper concentrations in wildtype and the ΔcsoR mutant in response to different copper amounts demonstrated an indirect relation between copper and iron. Further, ΔcsoR mutant exhibited differential regulation of oxygen sensing, cytochromes and anaerobic genes in response to excess copper in the growth media suggesting a probable role for CsoR and its significance in energy generation, cellular respiration, oxygen transport, and iron acquisition under different oxygen availability conditions imposed by the presence of copper.

Bibliographie / References

1. Reto Portmann, Kristian R. Poulsen, Reinhard Wimmer & Marc Solioz. CopY-like copper inducible repressors are putative 'winged helix' proteins. BioMetals (2006) 19: 61–70
2. Rick W. Ye, Wang Tao, Laura Bedzyk, Thomas Young, Mario chen, and Liao Li. Global Gene Expression Profiles of Bacillus subtilis Grown under Anaerobic Conditions. Journal of Bacteriology, Aug. 2000, p. 4458–4465.
3. Sylvia Franke, Gregor Grass, Christopher Rensing, and Dietrich H. Nies. Molecular Analysis of the Copper-Transporting Efflux System CusCFBA of Escherichia coli. Journal of Bacteriology. July 2003, p. 3804–3812
4. Michael Lacelle, Miyuki Kumano, Kenji Kurita, Kunio Yamane, Peter Zuber and Michiko M. Nakano. Oxygen-Controlled Regulation of the Flavohemoglobin Gene in Bacillus subtilis. Journal of Bacteriology, July 1996, p. 3803–3808
5. Ming Zheng, Bernard Doan, Thomas D. Schneider, and Gisela Storz. OxyR and SoxRS Regulation of fur. Journal of Bacteriology, Aug. 1999, p. 4639–4643
6. David Magnani & Marc Solioz. Copper chaperone cycling and degradation in the regulation of the cop operon of Enterococcus hirae. BioMetals (2005) 18:407–412.
7. N. A. Larsen, H. Lin, R. Wei, M. A. Fischbach, and C. T. Walsh. Structural Characterization of Enterobactin Hydrolase IroE. Biochemistry 2006, 45, 10184-10190
8. Daniel Strausak and Marc Solioz. CopY Is a Copper-inducible Repressor of the Enterococcus hirae Copper ATPases. The Journal of Biological Chemistry. Vol. 272, No. 14, Issue of April 4, pp. 8932–8936, 1997
9. Marcus Miethke, Oliver Klotz, Uwe Linne, Jürgen J. May, Carsten L. Beckering and Mohamed A. Marahiel. Ferri-bacillibactin uptake and hydrolysis in Bacillus subtilis. Molecular Microbiology (2006) 61(6), 1413–1427.
10. Fabio Arnesano, Lucia Banci, Manuela Benvenuti, Ivano Bertini, Vito Calderone, Stefano Mangani, and Maria Silvia Viezzoli. The Evolutionarily Conserved Trimeric Structure of CutA1 Proteins Suggests a Role in Signal Transduction. The Journal of Biological Chemistry. Vol. 278, No. 46, Issue of November 14, pp. 45999–46006, 2003
11. Fabio Arnesano, Lucia Banci, Ivano Bertini, Francesca Cantini, Simone Ciofi- Baffoni , David L. Huffman, and Thomas V. O'Halloran. Characterization of the Binding Interface between the Copper Chaperone Atx1 and the First Cytosolic Domain of Ccc2 ATPase. The Journal Of Biological Chemistry., Vol. 276, No. 44, Issue of November 2, pp. 41365–41376, 2001.
12. Yih-Chern Horng, Paul A. Cobine, Andrew B. Maxfield, Heather S. Carr, and Dennis R. Winge. Specific Copper Transfer from the Cox17 Metallochaperone to Both Sco1 and Cox11 in the Assembly of Yeast Cytochrome c Oxidase. The Journal Of Biological Chemistry. Vol. 279, No. 34, Issue of August 20, pp. 35334–35340, 2004
13. Hugo Cruz Ramos, Laurent Boursier,Ivan Moszer, Frank Kunst,Antoine Danchin and Philippe Glaser. Anaerobic transcription activation in Bacillus subtilis: identification of distinct FNR-dependent and -independent regulatory mechanisms. The EMBO Journal vol.14 no.23 pp.5984-5994, 1995
14. Joe M. Mccords and Irwin Fridovich. An Enzymic Function For Erythrocuprein (Hemocuprein). Superoxide Dismutase. The Journal Of Biological Chemistry., Vol. 244, No. 22, Issue of November 25, PP. 6049-6065, 1969
15. Isabell R. Loftin, Sylvia Franke, Sue A. Roberts, Andrzej Weichsel, Annie Heroux, William R. Montfort, Christopher Rensing, and Megan M. McEvoy. A Novel Copper-Binding Fold for the Periplasmic Copper Resistance Protein CusF. Biochemistry 2005, 44, 10533-10540.
16. Heike Reents, Ines Gruner, Ute Harmening, Lars H. Böttger, Gunhild Layer, Peter Heathcote, Alfred X. Trautwein, Dieter Jahn and Elisabeth Härtig . Bacillus subtilis Fnr senses oxygen via a [4Fe-4S] cluster coordinated by three cysteine residues without change in the oligomeric state. Molecular Microbiology (2006).
17. Christopher D. Vulpe and Seymour Packman. Cellular Copper Transport. Annu Rev.Nutr, 1995.1 5:293-322
18. Zouhair K. Attieh, Chinmay K. Mukhopadhyay, Vasudevan Seshadri, Nicholas A. Tripoulas, and Paul L. Fox. Ceruloplasmin Ferroxidase Activity Stimulates Cellular Iron Uptake by a Trivalent Cation-specific Transport Mechanism. The Journal Of Biological Chemistry., Vol. 274, No. 2, Issue of January 8, pp. 1116–1123, 1999.
19. Nathan E. Hellman and Jonathan D. Gitlin, Ceruloplasmin Metabolism and Function. Annu. Rev. Nutr. 2002. 22:439–58.
20. Maria Marjorette O. Pena, Sergi Puig, and Dennis J. Thiele. Characterization of the Saccharomyces cerevisiae High Affinity Copper Transporter Ctr3. The Journal Of Biological Chemistry., Vol. 275, No. 43, Issue of October 27, pp. 33244–33251, 2000
21. Angelica Reyesi, Andrea Leiva, Veronica Cambiazo, Marco A Mendez and Mauricio Gonzalez. Cop-like operon: Structure and organization in species of the Lactobacillale order. Biol Res 39: 87-93, 2006.
22. Edward D. Harris. Copper and Iron: A Landmark Connection of Two Essential Metals. The Journal of Trace Elements in Experimental Medicine 14:207–210 (2001).
23. Chean Eng Ooil, Efrat Rabinovich1 ,Andrew Dancis, Juan S.Bonifacinol and Richard D.Klausnerl. Copper-dependent degradation of the Saccharomyces cerevisiae plasma membrane copper transporter Ctrlp in the apparent absence of endocytosis. The EMBO Journal vol.15 no.14 pp.3515-3523, 1996
24. Marc Solioz , Jivko V. Stoyanov. 2003 Copper homeostasis in Enterococcus hirae FEMS Microbiology Reviews, 27. 183-195.
25. Anupama Shanmuganathana, Simon V. Averyb, Sylvia A. Willettsb, John E. Houghtona. Copper-induced oxidative stress in Saccharomyces cerevisiae targets enzymes of the glycolytic pathway. FEBS Letters 556 (2004) 253^259. References 107
26. Lucia Banci, Ivano Bertini, Rebecca Del Conte, Jacob Markey, and Francisco Javier Ruiz-Dueas. Copper Trafficking: the Solution Structure of Bacillus subtilis CopZ Biochemistry 2001, 40, 15660-15668.
27. Donald A. Cooksey. Copper uptake and resistance in bacteria. Molecular Microbiology (1993) 7(1), 1-5
28. Marc Solioz and Christopher Vulpe, CPx-type ATPases:a class of P-type ATPases that pump heavy metals. TIBS 21 -July 1996
29. Gregor Grass and Christopher Rensing. CueO Is a Multi-copper Oxidase That Confers Copper Tolerance in Escherichia coli. Biochemical and Biophysical Research Communications. Vol. 286, No. 5, 2001.
30. Yi Xue1, Anna V Davis, Gurusamy Balakrishnan, Jay P Stasser, Benjamin M Staehlin, Pamela Focia, Thomas G Spiro, James E Penner-Hahn & Thomas V O'Halloran. Cu(I) recognition via cation-p and methionine interactions in CusF. Nature Chemical Biology., Vol 4, No. 2, February 2008.
31. Christopher Stoj, Daniel J. Kosman. Cuprous oxidase activity of yeast Fet3p and human ceruloplasmin:implication for function. FEBS Letters 554 (2003) 422-426.
32. Ping Yu. Enhancing survival of Escherichia coli by increasing the periplasmic expression of Cu,Zn superoxide dismutase from Saccharomyces cerevisiae. Appl Microbiol Biotechnol (2007) 76:867–871
33. Christopher Rensing , Gregor Grass. Escherichia coli mechanisms of copper homeostasis in a changing environment. 2003. FEMS Microbiology Reviews 27 197- 213.
34. Richard Hassett and Daniel j. Kosman. Evidence for Cu(II) Reduction as a component of copper uptake by Saccharomyces cerevisiae. The Journal Of Biological Chemistry., Vol.270, No. 1 PP128-134. 1995
35. Michael G. Palmgren*, Kristian B. Axelsen. Evolution of P-type ATPases. 1998 Biochimica et Biophysica Acta, 1365, 37-45.
36. McIntosh. Export of the siderophore enterobactin in Escherichia coli: involvement of a 43 kDa membrane exporter. Molecular Microbiology (2002) 44(5), 1225–1234.
37. Hoch, J. A. 1991. Genetic analysis in Bacillus subtilis. Methods Enzymol.204:305– 320
38. Irene H. Hung, Ruby Leah B. Casareno, Gilles Labesse, F. Scott Mathews, and Jonathan D. Gitlin. HAH1 Is a Copper-binding Protein with Distinct Amino Acid Residues Mediating Copper Homeostasis and Antioxidant Defense. The Journal Of Biological Chemistry.,. Vol. 273, No. 3, Issue of January 16, pp. 1749–1754, 1998
39. Yuko Yamaguchi-Iwai, Mihaela Serpe, David Haile, Weimin Yang, Daniel J. Kosman, Richard D. Klausner, and Andrew Dancis. Homeostatic Regulation of Copper Uptake in Yeast via Direct Binding of MAC1 Protein to Upstream Regulatory Sequences of FRE1 and CTR1. The Journal Of Biological Chemistry., Vol. 272, No. 28, 17711–17718, 1997.
40. Leo W. J. Klomp, Su-Ju Lin, Daniel S.Yuan, Richard D. Klausner, Valeria Cizewski Culotta, and Jonathan D. Gitlin. Identification and Functional Expression of HAH1, a Novel Human Gene Involved in Copper Homeostasis. The Journal Of Biological Chemistry., Vol. 272, No. 14, Issue of April 4, pp. 9221–9226, 1997.
41. Alex Oddermath , Reto Krapf and Marc Soliz. Induction of putative copper ATPases CopA and CopB of Enterococcus hirae by Ag+ and Cu+ and extrusion by CopB. Biochemical and Biophysical Research Communications. Vol 202. No 1, July 15, 44- 48,1994.
42. Tsuyoshi Kimura, Hajime Nishioka. Intracellular generation of superoxide by copper sulphate in Escherichia coli. Mutation Research 389_1997.237–242.
43. Michiko M. Nakano and Yi Zhu. Involvement of ResE Phosphatase Activity in Down- Regulation of ResD-Controlled Genes in Bacillus subtilis during Aerobic Growth. Journal of Bacteriology, Mar. 2001, p. 1938–1944.
44. Colin Ratledge and Lynn G Dover. Iron Metabolism In Pathogenic Bacteria. Annu. Rev. Microbiol. 2000. 54:881–941
45. Daniele Touati, Micheline Jacques, Brigitte Tardat, Laurence Bouchard, and Sophie Despied. Lethal Oxidative Damage and Mutagenesis Are Generated by Iron in Dfur Mutants of Escherichia coli: Protective Role of Superoxide Dismutase. Journal of Bacteriology . May 1995, p. 2305–2314.
46. Lucia Banci, Ivano Bertini, Simone Ciofi-Baffoni, Theodoros Hadjiloi, Manuele Martinelli, and Peep Palumaa. Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer PNAS. May 13, 2008 _ vol. 105 _ no. 19 _ 6803–6808.
47. Laran T. Jensen, Matthew C. Posewitz, Chandra Srinivasan, and Dennis R. Winge. Mapping of the DNA Binding Domain of the Copper-responsive Transcription Factor Mac1 from Saccharomyces cerevisiae. The Journal of Biological Chemistry. Vol. 273, No. 37, Issue of September 11, pp. 23805–23811, 1998.
48. Byung-Eun Kim, Tracy Nevitt & Dennis J Thiele. 2008 Mechanisms for copper acquisition, distribution and regulation Nature Chemical Biology., Vol 4 Number 3 March.176-185.
49. Nathan E. Hellman, Satoshi Kono, Grazia M. Mancini, A. J. Hoogeboom, G. J. de Jong, and Jonathan D. Gitlin. Mechanisms of Copper Incorporation into Human Ceruloplasmin. The Journal Of Biological Chemistry., Vol. 277, No. 48, Issue of November 29, pp. 46632–46638, 2002.
50. Winge. Metalloregulation of FRE1 and FRE2 Homologs in Saccharomyces cerevisiae. The Journal Of Biological Chemistry., Vol. 273, No. 37, Issue of September 11, pp. 23716–23721, 1998.
51. David P. Giedroc and Alphonse I. Arunkumar. Metal sensor proteins: nature's metalloregulated allosteric switches. The Royal Society of Chemistry 2007 Dalton Trans., 2007, 3107–3120
52. Andrew Dancis, Daniel S. Yuan, David Haile, Candice Askwith,t David Eide, Charles Moehle,Jerry Kaplan,T and Richard D. Klausner. Molecular Characterization of a Copper Transport Protein in S. cerevisiae: An Unexpected Role for Copper in Iron Transport. Cell, Vol. 76, 393-402, January 28, 1994.
53. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY 102. Wach, A. 1996. PCR-synthesis of marker cassettes with long flanking homology 15 regions for gene disruptions in S. cerevisiae. Yeast 12:259–265.
54. Nigel L. Brown, Siobhan R. Barrett, James Camakaris, Barry T. O. Lee and Duncan A. Rouch . Molecular genetics and transport analysis of the copper-resistance determinant (pco) from Escherichia coil plasmid pRJ1004. Molecular Microbiology (1995) 17(6), 1153-1166
55. Michael J. Crawford and Daniel E. Goldberg. Regulation of the Salmonella typhimurium Flavohemoglobin Gene. A New Pathway For Bacterial Gene Expression In Response To Nitric Oxide. The Journal Of Biological Chemistry., Vol. 273, No. 51, Issue of December 18, pp. 34028–34032, 1998
56. Lilliana Quintanar, Christopher Stoj, Alexander B. Taylor, P. John Hart, Daniel J. Kosman, and Edward I. Solomon. Shall We Dance? How A Multicopper Oxidase Chooses Its Electron Transfer Partner. Acc. Chem. Res. 2007, 40, 445–452
57. Christopher S. Stoj, Anthony J. Augustine, Lynn Zeigler, Edward I. Solomon, and Daniel J. Kosman. Structural Basis of the Ferrous Iron Specificity of the Yeast Ferroxidase, Fet3p Biochemistry 2006, 45, 12741-12749.
58. Yu Hirano, Md. Motarab Hossain,Kazuki Takeda, Hajime Tokuda, and Kunio Miki, Structural Studies of the Cpx Pathway Activator NlpE on the Outer Membrane of Escherichia coli. Structure 15, 963–976, August 2007
59. Studied Biology and Chemistry as main subjects in high school at Chaitanya kalasala, Hyderabad, India in the year 1997.
60. Studied Microbiology, Biochemistry and Chemistry as main subjects in Graduation at Human Resources Development Degree College, Hyderabad, India from 1997-2000
61. Jorg Stulker, Enateh Anschke and Michaelh Ecker. Temporal activation of β- glucanase synthesis in Bucilfus subtilis is mediated by the GTP pool. Journal of General Microbiology (1 993), 139, 204 1-2045.
62. Jurgen J. May, Thomas M. Wendrich, and Mohamed A. Marahiel. The dhb Operon of Bacillus subtilis Encodes the Biosynthetic Template for the Catecholic Siderophore 2,3-Dihydroxybenzoate-Glycine-Threonine Trimeric Ester Bacillibactin. The Journal Of Biological Chemistry., Vol. 276, No. 10, Issue of March 9, pp. 7209–7217, 2001
63. Zen Huat Lu, Charles T. Dameron & Marc Solioz, The Enterococcus hirae paradigm of copper homeostasis: Copper chaperone turnover, interactions, and transactions. BioMetals 16: 137–143, 2003.
64. James P. Kehrer. The Haber–Weiss reaction and mechanisms of toxicity. Toxicology 149 (2000) 43–50
65. Andrew Dancis, David Haile, Daniel S. Yuan, and Richard D. Klausnert. The Saccharomyces cereuisiae Copper Transport Protein (Ctrlp), Biochemical Charecterisation, Regulation By Copper, And Physiological Role In Copper Uptake. The Journal Of Biological Chemistry., Vol. 269, No. 41, 25660-25667, 1994.
66. Lucia Banci, Ivano Bertini, Simone Ciofi-Baffoni, Rebecca Del Conte, and Leonardo Gonnelli. Understanding Copper Trafficking in Bacteria: Interaction between the Copper Transport Protein CopZ and the N-Terminal Domain of the Copper ATPase CopA from Bacillus subtilis. Biochemistry 2003, 42, 1939-1949
67. Jonas T. Larsson, Annika Rogstam and Claes von Wachenfeldt. Coordinated patterns of cytochrome bd and lactate dehydrogenase expression in Bacillus subtilis. Microbiology (2005), 151, 3323–3335
68. F. Wayne Outten, Caryn E. Outten, Jeremy Hale, and Thomas V. O'Halloran. Transcriptional Activation of an Escherichia coli Copper Efflux Regulon by the Chromosomal MerR Homologue, CueR. The Journal Of Biological Chemistry . Vol. 275, No. 40, pp. 31024–31029, 2000
69. Christopher J. Kershaw, Nigel L. Brown, Chrystala Constantinidou, Mala D. Patel and Jon L. Hobman. 2005. The expression profile of Escherichia coli K-12 in response to minimal, optimal and excess copper concentrations . Microbiology , 151, 1187–1198
70. Michiko M. Nakano, Tamara Hoffmann, Yi Zhu, and Dieter Jahn. Nitrogen and Oxygen Regulation of Bacillus subtilis nasDEF Encoding NADH-Dependent Nitrite Reductase by TnrA and ResDE. Journal of Bacteriology, Oct. 1998, p. 5344–5350.
71. Maria Marjorette O. Pena, Keith A. Koch, and Dennis J. Thiele, Dynamic Regulation of Copper Uptake and Detoxification Genes in Saccharomyces cerevisiae. Molecular and Cellular Biology., May 1998, p. 2514–2523.
72. Laran T.Jensen and Dennis R.Winge. Identification of a copper-induced intramolecular interaction in the transcription factor Mac1 from Saccharomyces cerevisiae. The EMBO Journal, Vol.17, No.18 pp.5400–5408, 1998.
73. Corinna Bleue, Cornelia Große, Nadine Taudte, Judith Scherer, Dirk Wesenberg, Gerd J. Krauß, Dietrich H. Nies, and Gregor Grass. TolC Is Involved in Enterobactin Efflux across the Outer Membrane of Escherichia coli. Journal of Bacteriology, Oct. 2005, p. 6701–6707
74. Sharon La Fontaine, Jeanette M. Quinn, Stacie S. Nakamoto, M. Dudley Page, Vera Gohre, Jeffrey L. Moseley, Janette Kropat, and Sabeeha Merchant. Copper- Dependent Iron Assimilation Pathway in the Model Photosynthetic Eukaryote Chlamydomonas reinhardtii. Eukaryotic Cell, Oct. 2002, p. 736–757
75. Greg Keller, Amanda Bird, and Dennis R. Winge. Independent Metalloregulation of Ace1 and Mac1 in Saccharomyces cerevisiae. Eukaryotic Cell, Nov. 2005, p. 1863–1871
76. Lars Hederstedt, Anna Lewin, and Mimmi Throne-Holst. Heme A Synthase Enzyme Functions Dissected by Mutagenesis of Bacillus subtilis CtaA. Journal of Bacteriology, Dec. 2005, p. 8361–8369
77. Juliane Ollinger, Kyung-Bok Song, Haike Antelmann, Michael Hecker, and John D. Helmann. Role of the Fur Regulon in Iron Transport in Bacillus subtilis. Journal of Bacteriology, May 2006, p. 3664–3673
78. K. Hantke, G. Nicholson, W. Rabsch, and G. Winkelmann. Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN. PNAS April 1, 2003 vol. 100 no. 7 3677–3682.
79. Smita Gyan, Yoshihiko Shiohira, Ichiro Sato, Michio Takeuchi, and Tsutomu Sato. Regulatory Loop between Redox Sensing of the NADH/NAD_ Ratio by Rex (YdiH) and Oxidation of NADH by NADH Dehydrogenase Ndh in Bacillus subtilis. Journal of Bacteriology, Oct. 2006, p. 7062–7071
80. Sita D. Gupta, Barry T. O. Lee, James Camakaris, and Henry C. Wui. Identification of cutC and cutF (nlpE) Genes Involved in Copper Tolerance in Escherichia coli. Journal of Bacteriology, Aug. 1995, p. 4207–4215
81. Timothy J. Tetaz and Richard K.J. Luke. Plasmid-Controlled Resistance to Copper in Escherichia coli. Journal of Bacteriology, June 1983, p. 1263-1268
82. Shashi Chillappagari, Marcus Miethke, Hein Trip, Oscar P. Kuipers, and Mohamed A. Marahiel. Copper Acquisition Is Mediated by YcnJ and Regulated by YcnK and CsoR in Bacillus subtilis. Journal of Bacteriology, Apr. 2009, p. 2362–2370
83. Lee Macomber and James A. Imlay1. The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity. 8344–8349 _ PNAS _ May 19, 2009 _ vol. 106 _ no. 20
84. Jody B. Proescher, Marjatta Son, Jeffrey L. Elliott and Valeria C. Culotta. Biological effects of CCS in the absence of SOD1 enzyme activation: implications for disease in a mouse model for ALS. Human Molecular Genetics, 2008, Vol. 17, No. 12 1728–1737.
85. Gregory T. Smaldone and John D. Helmann. CsoR regulates the copper efflux operon copZA in Bacillus subtilis. Microbiology (2007), 153, 4123–4128
86. Matthew Schau, Yinghua Chen, and F. Marion Hulett. Bacillus subtilis YdiH Is a Direct Negative Regulator of the cydABCD Operon. Journal of Bacteriology, July 2004, p. 4585–4595
87. Gregor Grass, Keshari Thakali, Phillip E. Klebba, Daniel Thieme, Axel Muller, Gunter F. Wildner, and Christopher Rensing. Linkage between Catecholate Siderophores and the Multicopper Oxidase CueO in Escherichia coli. Journal of Bacteriology, Sept. 2004, p. 5826–5833
88. Jae-Soon Cha and Donald A. Cooksey. Copper resistance in Pseudomonas syringae mediated by periplasmic and outer membrane proteins. Proc. Nati. Acad. Sci. USA. Microbiology Vol. 88, pp. 8915-8919, October 1991
89. Gregor Grass and Christopher Rensing. Genes Involved in Copper Homeostasis in Escherichia coli. Journal of Bacteriology, Mar. 2001, p. 2145–2147.
90. Kristian B. Axelsen, Michael G. Palmgren. 1998. Evolution of Substrate Specificities in the P-Type ATPase Superfamily J Mol Evol 46:84–101.

Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten