Research Summary

Many essential biological processes rely on the special catalytic properties of iron and thus this element is a required mineral nutrient for most organisms from bacteria to mammals. In key environments, growth of microorganisms is limited by the availability of iron. For example, humans have several systems that sequester iron to limit its availability to invading pathogens that are referred to as nutritional immunity. We are investigating systems used by bacterial pathogens such Staphylococcus aureus to overcome iron restriction and cause disease.

Many regions of the open ocean are iron limited receiving periodic inputs from terrestrial dust or deep water upwelling. A central focus my research is the investigation of the mechanism of iron uptake and storage systems in bacteria, yeast and diatoms employed to succeed in iron poor environments. We are combining structure determination by x-ray crystallography with biochemical and microbial approaches to define the molecular basis of iron uptake and storage.

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Technologies & Methods

For a complete list of publications, see my Google Scholar profile page.

Selected Recent Publications:

  1. Bowden, C.M.F., Verstraete, M.M., Eltis, L.D. & Murphy, M.E.P. (2014) The IsdB NEAT domain 1 of Hemoglobin binding and catalytic heme extraction by IsdB NEAT domains. Biochemistry. 53, 2286-94.
  2. Kobylarz, M.J., Grigg, J.C., Takayama, S.J., Rai, D.Y., Heinrichs, D.E., and Murphy, M.E.P. (2014) Synthesis of L-2,3-diaminopropionic acid, a siderophore and antibiotic precursor. Chem. & Biol. (Cell Press). 21, 379-88.
  3. Saer, R.G., Pan, J., Hardjasa, A., Lin, S., Rosell, F., Mauk, A.G., Woodbury, N.W., Murphy, M.E.P. & Beatty, J.T. (2014) Structural and kinetic properties of Rhodobacter sphaeroides photosynthetic reaction centers containing exclusively Zn-coordinated bacteriochlorophyll as bacteriochlorin cofactors. Biochem. Biophys. ACTA. 1837, 366-74.
  4. De, S., Chan, A.C.K., Coyne, H.J., Okon, M., Murphy, M.E.P., Graves, B.J. and McIntosh, L.P. (2014) Steric mechanism of auto-inhibition regulation of specific and non-specific DNA binding by the ETS transcriptional repressor ETV6. J. Mol. Biol. 426, 1390-406.
  5. Loutet, S.A., Kobylarz, M.J. Chau, C.H.T. & Murphy, M.E.P. (2013) IruO is a reductase for heme degradation by IsdI and IsdG proteins in Staphylococcus aureus. J. Biol. Chem. 288, 25749-59.
  6. Pfaffen, S., Abdulqadir, R., Le Brun, N.E. & Murphy M.E.P. (2013) Mechanism of ferrous iron binding and oxidation by ferritin from a pennate diatom. J. Biol. Chem. 288, 14917-25.
  7. Saer, R.G., Hardjasa, A., Rosell, F., Mauk, A.G., Murphy, M.E.P. & Beatty, J.T. (2013) The role of Rhodobacter sphaeroides photosynthetic reaction center residue M214 amino acid in the composition, light-absorption properties, and conformations of HA and BA cofactors. Biochemistry 52, 2206-17.
  8. Singh, R., Grigg, J.C., Wei, Q., Kadla, J.F., Murphy, M.E.P. & Eltis, L.D. (2013) Improved manganese-oxidizing activity of DypB, a peroxidase from a lignolytic bacterium. ACS Chem. & Biol. 8, 700-6.
  9. Cadieux, B., Lian, T., Hu, G., Wang, J., Biondo, C., Teti, G., Liu, V., Murphy, M.E.P., Creagh, A.L. & Kronstad, J.W. (2013) The mannoprotein Cig1 supports iron acquisition from heme and virulence in the pathogenic fungus Cryptococcus neoformans. J. Infect. Dis. 207, 1339-47.
  10. Cheung, J., Murphy, M.E.P. & Heinrichs, D.E. (2012) Discovery of a novel, iron-regulated citrate synthase in Staphylococcus aureus. Chem. & Biol. (Cell press), 19, 1568-78.
  11. Ukpabi, G., Takayama, S.J., Mauk, A.G. & Murphy, M.E.P. (2012) Inactivation of IsdI heme oxidation by an active site substitution that diminishes heme ruffling. J. Biol. Chem. 287, 34179-88.
  12. Freeman, J.O., Murphy, M.E.P. & Sherman, J.C. (2012) Monomer-dimer control and crystal engineering in TASPs. Chemistry. 18, 11409-16.
  13. Singh, R., Grigg, J.C., Armstrong, Z., Murphy, M.E.P. & Eltis, L.D. (2012) The distal heme pocket residues of a B-type dye-decolorizing peroxidase: arginine but not aspartate is essential for peroxidase activity. J. Biol. Chem. 287, 10623-30.
  14. Grigg, J.C., Mao, C.X., & Murphy, M.E.P. (2011) Iron coordinating tyrosine is a key determinant of NEAT domain heme transfer. J. Mol. Biol. 413: 684-98.
  15. Takayama, S.J., Ukpabi, G., Murphy*, M.E.P. & Mauk*, A.G. (2011) Electronic properties of the highly ruffled heme center of the heme degrading enzyme IsdI. Proc. Nat. Acad. Sci., 108: 13071-6.
  16. Koch, D., Chan, A.C.K., Murphy, M.E.P., Lilie, H., Grass, G. & Nies, D.H. (2011) Characterization of a novel dipartite iron uptake system from uropathogenic Escherichia coli strain F11. J. Biol. Chem. 286, 25317-30.
  17. Gaudin, C.F.M., Grigg, J.C., Arrieta, A.L., & Murphy, M.E.P. (2011) Unique axial tyrosine and methionine heme iron coordination in a NEAT domain from Staphylococcus aureus IsdB. Biochemistry, 50, 5443-52. (Citations 24)
  18. Roberts, J.N., Singh, R., Grigg, J.C., Murphy, M.E.P., Bugg, T.D.H. and Eltis, L.D. (2011) Characterization of DyP peroxidases from Rhodococcus jostii RHA1. Biochemistry, 50, 5108-19. (Citations 23)
  19. Grigg, J.C., Cheung, J., Heinrichs, D.E., Murphy, M.E.P. (2010) Specificity of staphyloferrin B recognition by the SirA receptor from Staphylococcus aureus. J. Biol. Chem. 285, 34579-88. (Citations 21)
  20. Chan, A.C.K., Doukov, T.I, Scofield, M., Tom-Yew, S.A.L., Ramin, A., MacKichan, J.K., Gaynor, E.C. & Murphy. M.E.P. (2010) Structure and function of P19, a high affinity iron transporter of the human pathogen Campylobacter jejuni. J. Mol. Biol. 401, 590-604.
  21. Grigg, J.C., Cooper, J.D., Cheung, J., Heinrichs, D.E., Murphy, M.E.P. (2010) The Staphylococcus aureus siderophore receptor, HtsA, undergoes localized conformational changes to enclose staphyloferrin A in an Arg-rich binding pocket. J. Biol. Chem. 285, 11162-71. (Citations 30)
  22. Reniere, M.L., Ukpabi, G., Harry, S.R., Stec, D.F., Wright, D.W., Bachmann, B.O., Murphy, M.E.P., Skaar, E.P. (2010) A conserved heme oxygenase from pathogenic bacteria degrades heme to a novel chromophore. Mol. Microbiol. 75, 1529-38. (Citations 46)
  23. MacPherson, I.S, Rosell, F.I., Scofield, M., Mauk, A.G. & Murphy, M.E.P. (2010) Directed evolution of copper nitrite reductase to a chromogenic reductant. Prot. Eng. Design Sel. 24, 137-45.
  24. Wong, S.G., Tom-Yew, S.A.L., Lewin, A.C., Le Brun, N., Moore, G.R., Murphy, M.E.P. & Mauk, A.G. (2009) Structural and mechanistic studies of a stabilized subunit dimer variant of Escherichia coli bacterioferritin identify residues required for core formation. J. Biol. Chem. 284, 18873-81.
  25. Freeman, J.O., Lee, W.C., Murphy, M.E.P. & Sherman, J.C. (2009) X-ray crystal analysis of a TASP: structural insights of a cavitein dimer. J. Amer. Chem. Soc. 131, 7421-9.
  26. Zhao, L., Nguyen, N.T., Fernandez, R.C. & Murphy, M.E.P. (2009) Crystallographic characterization of the passenger domain of the Bordetella autotransporter BrkA. Acta Crystallogr. F. 65, 608-11.
  27. Beasley, F.C., Vines, E.D., Grigg, J.C., Zheng, Q., Murphy, M.E.P. & Heinrichs, D.E. (2009) Identification of a second genetic locus involved in siderophore biosynthesis in Staphylococcus aureus: characterization of siderophore biosynthetic and iron-siderophore transport mutants. Mol. Microbiol. 72, 947-63. (Citations 47)
  28. Marchetti, A., Parker, M.S., Moccia, L.P., Lin, E.O., Arrieta, A.L., Murphy, M.E.P., Maldonado, M.T. & Armbrust, E.V. (2009) Ferritin is used for iron storage in bloom-forming marine pennate diatoms. Nature 457, 467-470. (Citations 115)
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