College of Arts & Sciences

Dabney Dixon

Dabney White Dixon Professor Bioorganic Chemistry A.B. (1971):  Brown University Ph.D. (1976) :  Massachusetts Institute of Technology Postdoctoral Fellowship (1977-1978) :  University of California, San Diego Dr. Dabney White Dixon Department of Chemistry Georgia State University P.O. Box 4098 Atlanta, Georgia 30302-4098 Department Office Phone: 404-413-5500 Hours: M-F 9am - 5:30pm Phone:  404-413-5508 Lab Phone:  404-413-5548 Fax:  404-413-5505 Office:  556 Natural Science Center Email:  ddixon@gsu.edu

For STEM education resources, please visit: http://www.cas.gsu.edu/stem.html.

Research in the Dixon Laboratory

Heme Uptake by Pathogenic Bacteria.  A number of pathogenic bacteria grow with hemin as their major or sole source of iron. Streptococcus pyogenes is one of only of the comparatively small number of bacteria that can only obtain heme from its environment. S. pyogenes, also known as Group A streptococcus (GAS), is a pathogenic Gram positive bacterium that causes a variety of infections. S. pyogenes is increasingly resistant to antibiotics, potentially posing significant risks for infected populations.

In S. pyogenes, one pathway for heme import is through an ATP binding cassette. This has been termed the streptococcal iron acquisition or Sia system. In this ABC transporter, SiaA is the lipoprotein-anchored heme binding protein that acquires heme and transfers it to the SiaB which in turn carries the heme across the lipid bilayer. In this process energy is provided from ATP hydrolysis by SiaC, which is located in the inner side of the membrane. We are performing biophysical characterization of the protein in terms of the factors that control heme uptake and release. The main contributors are nature of the axial ligand, electrostatic interactions with the heme propionates and the iron center and hydrophobic interactions to control heme uptake and release.

We are also studying heme uptake in Corynebacterium diphtheriae, the causative agent of diphtheria. This pathway, also an ABC transporter, bears superficial resemblance to that of S. pyogenes, but varies significantly in the details.

DNA Intercalators.  Intercalators are flat molecules that slide between the base pairs of duplex DNA. We are studying the fundamental factors that control DNA intercalation. Our most recent work involves the binding of four homologous anthraquinones (AQ) bearing polyethylene glycol-based side chains to both AT- and GC-rich hairpins. The binding affinity and thermodynamic parameters have been assessed via circular dichroism, surface plasmon resonance and isothermal titration calorimetry measurements. Binding of intercalators to DNA can be parsed in terms of a series of free energy contributions, including the free energy contribution from conformational changes in the DNA and ligand upon binding. Conformational changes for intercalators binding to DNA are often neglected, both because many intercalators do not have significant numbers of rotatable bonds, and because T∆S for many is small. Our work shows that there is a measurable entropic cost when intercalators with long side chains bind to DNA. This is greater the longer the side chain and is significant enough to cause a decrease in DNA binding affinity. The importance of entropic considerations is also seen in the observation that DNA binding of intercalators shows more dependence on the number of rotatable bonds in the side chain than on the hydrophobicity of the ligand. Our binding shows significant enthalpy-entropy compensation. Enthalpy-entropy compensation is a complex phenomenon, involving not only noncovalent interactions between the ligand and DNA, but also rearrangement of the water molecules involved in the complex with the resulting changes in hydrogen bonding.

Publications since 2000

Weiner, S. W., Cerpovitz, P. F., Dixon, D. W., Harden, D. B., Hobbs, D. S., and Gosnell, D. L. (2000).  RasMol and Mage in the undergraduate biochemistry curriculum.  J. Chem. Educ. 77, 401-406.

Genco, C. A. and Dixon, D. W. (2001).  Emerging strategies in microbial heme capture.  Mol. Microbiol. 39, 1-11.

Olczak, T., Dixon, D. W., and Genco, C. A. (2001).  Binding specificity of the Porphyromonas gingivalis hemoglobin and heme receptor HmuR, and its cooperation with gingipain K, a putative hemophore.  J. Bacteriol. 183, 5599-5608.

Vzorov, A. N., Dixon, D. W., Trommel, J. S., Marzilli, L. G., and Compans, R. W. (2002).  Inactivation of human immunodeficiency virus type 1 by porphyrins.  Antimicrob. Agents Chemother. 46, 3917-3925.

Chen-Collins, A. R. M., Dixon, D. W., Vzorov, A. N., Marzilli, L. G., and Compans, R. W. (2003).  Prevention of poxvirus infection by tetrapyrroles.  BMC Infect. Dis. 3, 9.

Vzorov, A. N., Marzilli, L. G., Compans, R. W., and Dixon, D. W. (2003).  Prevention of HIV-1 infection by phthalocyanines.  Antiviral Res. 59, 99-109.

Dixon, D. W., Gill, A. F., and Sook, B. R. (2004).  Characterization of sulfonated phthalocyanines by mass spectrometry and capillary electrophoresis.  J. Porph. Phthalo. 8, 1300-1310.

McKnight, R. E., Zhang, J., and Dixon, D. W. (2004).  Binding of a homologous series of anthraquinones to DNA.  Bioorg. Med. Chem. Lett. 14, 401-404.

Dixon, D. W., Gill, A. F., Giribabu, L., Vzorov, A. N., Alam, A. B., and Compans, R. W. (2005).  Sulfonated naphthyl porphyrins as agents against HIV.  J. Inorg. Biochem. 99, 813-821.

Liu, X. Y., Olczak, T., Guo, H. C., Dixon, D. W., and Genco, C. A. (2006).  Identification of amino acid residues involved in heme binding and hemoprotein utilization in the Porphyromonas gingivalis heme receptor HmuR.  Infect. Immun. 74, 1222-1232.

Dixon, D. W. (2007). Duplex DNA binding of nonplanar metal chelates of cationic porphyrins, in "Synthetic and Biophysical Studies of DNA Binding Compounds" (M. Lee and L. Strekowski, Eds.), pp. 239-262.

Vzorov, A. N., Bozja, J., Dixon, D. W., Marzilli, L. G., and Compans, R. W. (2007).  Parameters of inhibition of HIV-1 infection by anionic microbicides.  Antiviral Res. 73, 60-68.

Kim, M. B. and Dixon, D. W. (2008). Hydrolysis of aliphatic naphthalene diimides: Effect of charge placement in the side chains. J. Phys. Org. Chem. 21, 731-737.

Sook, B. R., Block, D. R., Sumithran, S., Montañez, G. E., Rodgers, K. R., Dawson, J. H., Eichenbaum, Z., and Dixon, D. W. (2008). Characterization of SiaA, a streptococcal heme-binding protein associated with a heme ABC transport system. Biochemistry 47, 2678-2688.

Abou-Elkhair, R. A. I., Dixon, D. W., and Netzel, T. L. (2009). Synthesis and electrochemical evaluation of conjugates between 2'-deoxyadenosine and modified anthraquinone: Probes for hole transfer studies in DNA. J. Org. Chem. 74, 4712-4719.

Cao, Y., Rabinowitz, D. J., Dixon, D. W., and Netzel, T. L. (2009). Synthesis, Electrochemistry, and Hydrolysis of Anthraquinone Derivatives. Synth. Commun. 39, 4230-4238.

Cao, Y., Gill, A. F., and Dixon, D. W. (2009). Synthesis and characterization of a water-soluble porphyrin with a cyclic sulfone. Tetrahedron Lett. 50, 4358-4360.

Laster, B. H., Dixon, D. W., Novick, S., Feldman, J. P., Seror, V., Goldbart, Z. I., and Kalef-Ezra, J. A. (2009). Photon activation therapy and brachytherapy. Brachytherapy 8, 324-330.

Ouattara, M., Cunha, E. B., Li, X., Huang, Y.-S., Dixon, D. W., and Eichenbaum, Z. (2010). Shr of Group A Streptococcus is a new type of composite NEAT protein involved in sequestering heme from methemoglobin. Mol. Microbiol. 78, 739-756.

McKnight, R. E., Reisenauer, E., Pintado, M. V., Polasani, S. R., and Dixon, D. W. (2011). Substituent effect on the preferred DNA binding mode and affinity of a homologous series of naphthalene diimides. Bioorg. Med. Chem. Lett. 21, 4288-4291.

Jackson Beckford, S. and Dixon, D. W. (2012). Molecular dynamics of anthraquinone DNA intercalators with polyethylene glycol side chains. J. Biomol. Struct. Dyn. 29, 1065-1079.