Skip to main content

Kenton Rodgers

Inorganic and Bioinorganic Chemistry

Research in my group is focused on the roles of transition metal ions in biology. Of particular interest are proteins and enzymes involved in biological CO, NO, and O2 sensing (Figures 1 & 2), activation of O2, heme transport in bacterial pathogens (Figures 3 & 4), and metal-dependent proteolysis (Figures 5 & 6). We bring a variety of chemical, spectroscopic, and computational methods to bear on questions of the interplay between structure, dynamics, and function of metalloproteins. Chemical methods include synthesis and characterization of model complexes, studies of reaction rates and mechanism, and protein expression and purification. Among the physical methods are resonance Raman, steady-state and transient UV-visible absorbance, circular dichroism, NMR, EPR, and crystallography. We use computational methods based on density functional theory and molecular mechanics force fields to gain insight into structure, bonding and reactivity of metal-containing protein active sites.

Figure 1.
Transient absorbance spectra used to determine rates of ligand rebinding to the heme and ligand-coupled conformational dynamics in O26 sensing protein, FixL.

Figure 2. HOMO of [Fe(por)NO]+, showing the Fe-N and N-O antibonding character of the {FeNO}6 moiety. We have shown that the behavior of these bonds is in contrast to the classical backbonding behavior in which the Fe-X and X-O bond strengths vary inversely. The FeNO antibonding character of the HOMO in these {FeNO}6 porphyrinates causes the Fe-N and N-O bond strengths to vary directly in response to both intra- and intermolecular influences.

Figure 3
. Cartoon illustrating the heme uptake and intracellular transport steps in iron assimilation by the bacterial pathogen, Shigella dysenteriae. We are working to understand the molecular mechanisms by which heme is transferred between the proteins that comprise this pathway.

Figure 4
. Resonance Raman spectra of the periplasmic heme binding protein, ShuT. Spectra of the wild type and Y94A mutants are shown. These spectra provide part of the evidence for assignment of the endogenous heme ligand, Tyr94.

Figure 5
. X-ray crystal structure of [TpPh,MeZn(2−ImPr)]. The bidentate 2−ImPr‾ ligand is rendered in ball-and-stick format. This complex is a structural mimic of the active sites in zinc-dependent metalloproteases of the metzincin class. We are designing and testing novel zinc chelating groups that could be conjugated to larger molecules to make a new generation of metzincin inhibitors. Such chemotherapeutic agents could be valuable in treating a variety of diseases, including cardiovascular disease, stroke, cancers, and arthritis.

Figure 6
. 500 MHz 1H NMR spectra tracking the titration of [TpPh,MeZnOH], a mimic of metzincin resting states, with HClO4 in CD3OD at 25 °C (middle and right panels). The left panel shows single-proton titration curves derived from the [H+] dependences of the 1Ha and 1Hc chemical shifts. Understanding the effects of acid-base interconversions on the NMR spectrum allows us to clearly identify the spectral changes associated with displacement of the hydroxide ligand by our zinc binding groups.

Selected Publications

Linder, D. P.; Rodgers, K. R. “Computational Modeling of Factors that Modulate the Unique FeNO Bonding in {FeNO}6 Heme-thiolate Model Complexes” J. Biol. Inorg. Chem. 2007, in press.

Nadia Izadi-Pruneyre, Frédéric Huché, Gudrun S. Lukat-Rodgers, Anne Lecroisey, Robert Gilli, Kenton R. Rodgers, Cécile Wandersman, and Philippe Delepelaire “Protein-protein interaction drives heme transfer from a high to a lower affinity binding site” J. Biol. Chem. 2006, 281, 25541-25550.

Ila B. Lansky, Gudrun S. Lukat-Rodgers, Darci Block, Kenton S. Rodgers, Melanie Ratliff, and Angela Wilks “The cytoplasmic heme-bindingpProtein (PhuS) from the heme uptake system of Pseudomonas aeruginosa is a heme chaperone to the δ-regioselective heme oxygenase” J. Biol. Chem. 2006, 281, 13652-13662.

Smith, J. M.; Sadique, A. R.; Cundari, T. R.; Kenton R. Rodgers, K. R.; Lukat-Rodgers, G. S.; Lachicotte, R. J.; Flaschenriem, C. J.; Vela, J.; Holland, P. L. “Studies of Low-coordinate Iron-dinitrogen Complexes” J. Am. Chem. Soc. 2006, 128, 756-769.

Pazicni, S.; Cherney, M. M.; Lukat-Rodgers, G. S.; Oliveriusová, J.; Rodgers, K. R.; Kraus, J. P.; Burstyn, J. N. “The Heme of Cystathionine β−synthase Undergoes a Thermally-induced Redox-mediated Ligand Switch” submitted to Biochemistry 2005, 44, 16785-16795.

Linder, D. P.; Rodgers, K. R. “Structural, Electronic, and Vibrational Characterization of Fe−HNO Porphyrinates by Density Functional Theory” Inorg. Chem. 2005, 44, 8259-8264.

Eakanunkul, S.; Lukat-Rodgers, G. S.; Sumithran, S.; Ghosh, A.; Rodgers, K. R.; Dawson, J. H.; Wilks, A. “Characterization of the Periplasmic Heme-binding Protein ShuT from the Heme Uptake System of Shigella dysenteriae” Biochemistry 2005, 44, 13179-13191.

He, H.; Puerta, D. T.; Cohen, S. M.; Rodgers, K. R. “A Structural and Spectroscopic Study of Reactions between Chelating Zinc-Binding Groups and Mimics of the MMP and ADAM Catalytic Sites: The Coordination Chemistry of Metalloprotease Inhibition” Inorg. Chem.2005, 44, 7431-7442.

Rodgers K. R., Lukat-Rodgers, G. S. “Insights into Heme-based O2 Sensing from Structure Function Relationships in the FixL Proteins” J. Inorg. Biochem. 2005, 99, 963-977.

Linder, D. P.; Rodgers, K. R. “Fe−N−O Structure and Bonding in Six-Coordinate {FeNO}6 Porphyrinates Containing Imidazole: Implications for Reactivity of Coordinated NO” Inorg. Chem. 2005, 44, 1367-1380.

Pazicni, S.; Lukat-Rodgers, G. S.; Oliveriusova, J; Rees, K. A.; Parks, R. B.; Clark, R. W.; Rodgers, K. R.; Kraus, J. P.; Burstyn, J. N. “The Redox Behavior of the Heme in Cystathionine β−synthase Is Sensitive to pH” Biochemistry 2004 43, 14684-14695.

Wengenack, N. L.; Lane, B. D.; Hill, P. J.; Uhl, J. R.; Lukat-Rodgers, G. S.; Hall, L.; Roberts, G, D.; Cockerill, F. R.; Brennan, P. J.; Rodgers, K. R.; Belisle, J. T.; Rusnak, F. “Purification and characterization of Mycobacterium tuberculosis KatG, KatG(S315T), and Mycobacterium bovis KatG(R463L)” Protein Expression and Purification 2004 36, 232-243.

Linder, D. P.; Rodgers, K. R. Banister, J.; Wyllie, G. R.; Ellison, M. K.; Scheidt, W. R. “FeIIINO and FeIICO Units in Five-Coordinate Iron Porphyrinates: Where are the Electrons and Why does it Matter?” J. Am. Chem. Soc. 2004, 126, 14136-14148.

Hao Zhu, H.; Larade, K.; Jackson, T. A.; Xie, J.; Ladoux, A.; Acker, H.; Berchner-Pfannschmidt, U.; Fandrey, J.; Cross, A. R.; Lukat-Rodgers, G. S.; Rodgers, K. R.; Bunn, H. F. “NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum” J. Biol. Chem. 2004, 279, 30316-30325.

Linder, D. P.; Rodgers, K. R. “A Theoretical Study of Imidazole- and Thiol-based Zinc Binding Groups Relevant to Matrix Metalloprotease Inhibition” J. Phys. Chem. B. 2004, 108, 133839-13849.

He, H.; Rodgers, K. R.; Arif, A. “Structural and Spectroscopic Studies of Tripodal [MgL]2+ Chelates Containing only Nitrogen Donor Atoms: Alkaline Earth Metal Complexes as Potential Drug Delivery Agents” J. Inorg. Biochem. 2004, 98, 667–676.

He, H.; Linder, D. P.; Rodgers, K. R.; Chakraborty, I.; Arif, A. “A Thiazole-containing Tripodal Ligand: Synthesis, Characterization, and Interactions with Metal Ions and Matrix Metalloproteinases” Inorg. Chem. 2004, 43, 2392-2401.

Cowley, A. B.; Lukat-Rodgers, G. S.; Rodgers, K. R.; Benson, D. R. “A Possible Role for the Covalent Heme-Protein Linkage in Cytochrome c Revealed via Comparison of N-Acetylemicroperoxidase-8 and a Synthetic Monohistidine-Coordinated Heme Peptide” Biochemistry 2004, 43, 1656-1666.

Rodgers K. R., Lukat-Rodgers, G. S. “Electron Transfer Cytochromes” In Comprehensive Coordination Chemistry II; McCleverty, J., Meyer, T. J., Eds.; Pergamon: Oxford, 2004; Vol. 8, pp. 17-60.



BS, University of Missouri Columbia, 1981
MS, University of Missouri - Columbia, 1982
Research Fellow, Montanuniversität, Austria, 1983
PhD University of Iowa, 1988
NIH Postdoctoral Fellow, Princeton University, 1989-1993

Office: 365 Dunbar

tel 701-231-8746
fax 701-231-8831