BS, 1998, University of Oklahoma PhD, 2003, OMRF and the OUHSC Postdoc, 2003-2007, OUHSC Associate Research Scientist, 2007-2013, Oklahoma State University

Our research interests are in the relation of protein function to macromolecular structure. We are integrating X-ray crystallography with microbiology and chemical biology to answer questions about toxin-antitoxin systems and other proteins, and their roles in bacteria that cause human disease.

Current projects include:

Analysis of Type II Toxin-Antitoxin systems in bacteria. A currently funded project focuses on understanding the mechanistic details of the ParE toxin inhibition of DNA gyrase and the impact of ParE sequence variability on that activity.

Fragment-based approaches to target bacterial folate biosynthetic enzymes. These projects are typically assigned to undergraduates, who then have the opportunity to discover new structural insights using recombinant protein production and X-ray crystallographic techniques.

Development of inhibitors of dihydrofolate reductase. This is an extension of previous work and is carried out with OSU collaborators to improved antibacterial compounds.

Building a forward chemical genetic system for compound target identification

Phenotypic screening / MIC assays

These projects utilize techniques spanning protein purification and crystallization, biophysical measurements, microbiology and molecular genetics, and structural biology – please see the lab webpage for more details.

Nammalwar, B., Bourne, C.R., Wakeham, N., Bourne, P.C., Barrow, E.W., Muddala, N.P, Bunce, R.A., Berlin, K.D., Barrow, W.W. (2015) Modified 2,4-diaminopyrimidine-based dihydrofolate reductase inhibitors as potential drug scaffolds against Bacillus anthracis. Bioorg. Med. Chem. 23:203-11. PMCID: PMC4278362

Kobayashi, M., Tomohiro, K., Koseki, Y., Bourne, C.R., Barrow, W., Aoki, S. (2014) Identification of novel potential antibiotics against Staphylococcus using structure-based drug screening targeting dihydrofolate reductase. J. of Chemical Information and Modelling, 28:1242-53.

Nammalwar, B., Muddala, N.P., Bourne, C.R., Henry, M., Bourne, P.C., Bunce, R.A., Barrow, E.W., Berlin, K.D., Barrow, W.W. (2014) Synthesis and biological evaluation of 2,4-diaminopyrimidine-based antifolate drugs against Bacillus anthracis. Macromolecules 19:3231. PMCID: PMC4016962

Bourne, C.R., Wakeham, N., Webb, N. Nammalwar, B., Bunce, R.A., Berlin, K.D., Barrow, W.W. (2014) Structure and competitive substrate inhibition of dihydrofolate reductase from Enterococcus faecalis reveals restrictions to co-factor docking. Biochemistry 53:1228-1238. PMCID: PMC3985486

Bourne, C.R. (2014) Utility of the biosynthetic folate pathway for targets in antimicrobial discovery. Antibiotics 3(1): 1-28.

Bourne, C.R., Wakeham, N., Nammalwar, B., Tseitin, V., Bourne, P.C., Barrow, E.W., Ramnarayan, K., Bunce, R.A., Berlin, K.D., Barrow, W.W. (2013) Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase. Biochimica et Biophysica Acta – Proteins and Proteomics epub Sept. 20, 2012. 1834:46-52. PMCID: PMC3530638

Nammalwar, B., Bunce, R. A., Berlin, K. D., Bourne, C. R., Bourne, P. C., Barrow, E. W., Barrow, W. W. (2013) Comparative Study of the Frech Catalyst with Two Conventional Catalysts in the Heck Synthesis of 2,4-Diaminopyrimidine-based Antibiotics. Organic Preparations and Procedures International. 45(1):66-71. PMC3683996

Nammalwar, B., Bourne, C.R., Bunce, R.A., Wakeham, N., Bourne, P.C., Ramnarayan, K., Mylvaganam, S., Berlin, K.D., Barrow, E.W., Barrow, W.W. (2012) Inhibition of bacterial dihydrofolate reductase by 6-Alkyl-2,4-diaminopyrimidines. ChemMedChem epub Aug. 28. 7:1974-82. PMCID: PMC3570588 *Featured on inside cover figure

Nammalwar, B., Bunce, R.A., Berlin, K.D., Bourne, C.R., Bourne, P.C., Barrow, E.W., Barrow, W.W. (2012) Synthesis and biological activity of substituted 2,4-diaminopyrimidines that inhibit Bacillus anthracis. European Journal of Medicinal Chemistry 54:387-96. PMCID: PMC3408765

Nammalwar, B., Bunce, R. A., Berlin, K. D., Bourne, C. R., Bourne, P. C., Barrow, E. W., Barrow, W. W. (2012) Microwave-assisted Heck synthesis of substituted 2,4-diaminopyrimidine-based antibiotics. Organic Preparations and Procedures International. 44(3):281-87. PMC3691060

Nammalwar, B., Bunce, R.A., Berlin, K.D., Bourne, C.R., Bourne, P.C., Barrow, E.W., Barrow, W.W. (2012) Approaches to iodinated derivatives of vanillin and isovanillin. Organic Preparations and Procedures International. 44(2):146-152. PMC3691065

Bourne, C.R., Barrow, E.W., Bunce, R.A., Bourne, P.C., Berlin, K.D., Barrow, W.W. (2010) Inhibition of antibiotic resistant Staphylococcus aureus by the broad-spectrum dihydrofolate reductase inhibitor RAB1. Antimicrobial Agents and Chemotherapy 54(9): 3825-33. PMCID: PMC2934973

Bourne, C. R., Bunce, R. A., Bourne, P. C., Berlin, K. D., Barrow, E. W., Barrow, W. W. (2009) Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity. Antimicrobial Agents and Chemotherapy 53(7): 3065-73. PMCID: PMC2704665

Barrow, E.W., Clinkenbeard, P.A., Duncan-Decocq, R.A., Perteet, R.F., Hill, K.D., Bourne, P.C., Valderas, M.W., Bourne, C.R., Clarkson, N.L., Clinkenbeard, K.D., Barrow, W.W. (2012) High-throughput screening of a diversity collection using biodefense category A and B Priority pathogens. Journal of Biomolecular Screening 17(7):946-56. PMCID: PMC3700734

Bourne, C.R., Wakeham, N., Bunce, R.A., Nammalwar, B., Berlin, K.D., Barrow, W.W. (2012) Classifying compound mechanism of action for linking whole cell phenotypes to molecular targets. Journal of Molecular Recognition 25:216-23. PMCID: PMC3703735

Bourne, C. R., Katen, S. P., Fulz, M. R., Packianathan, C., Zlotnick, A. (2009) A mutant Hepatitis B virus core protein mimics inhibitors of icosahedral capsid self-assembly. Biochemistry, 48(8): 1736-42. PMCID: PMC2880625

Bourne, C., Lee, S., Venkataiah, B. Lee, A., Korba, B., Finn, M.G., Zlotnick, A. (2008) Small-molecule effectors of Hepatitis B virus capsid assembly give insight into virus lifecycle. Journal of Virology 82(20): 10262-70. PMCID: PMC2566253

Zlotnick, A., Lee, A., Bourne, C. R., Johnson, J. M., Domanico, P. L., Stray, S. J. (2007) In vitro screening for molecules that affect virus capsid assembly and other protein association reactions. Nature Protocols 2(3): 490-98. PMCID: PMC2099249 *Cover figure from this manuscript

Bourne, C. R., Finn, M. G., Zlotnick, A. (2006) Global structural changes in hepatitis B capsids induced by the assembly effector HAP1. Journal of Virology 80(22): 11055-61. PMCID: PMC1642186

Stray, S. J., Bourne, C. R., Punna, S., Lewis, W. G., Finn, M. G., Zlotnick, A. (2005). A heteroaryldihydropyrimidine activates and can misdirect Hepatitis B virus capsid assembly. Proceedings of the National Academies of Science USA, 102(23): 8138-40. PMCID: PMC1149411