W. David Tolbert Email & Phone Number

Bethesda, Maryland

Scientist IHenry M Jackson FoundationInfectious Disease DivisionDepartment of MedicineUniformed Services University of the Health Sciences

Baltimore, Maryland Area

Baltimore, Maryland Area

Gohain, N., Tolbert, W. D., Acharya, P., Yu, L., Liu, T., Zhao, P., Orlandi, C., Visciano, M. L., Kamin-Lewis, R., Sajadi, M. M., Martin, L., Robinson, J. E., Kwong, P. D., DeVico, A. L., Ray, K., Lewis, G. K., Pazgier, M. “Co-crystal structures of antibody N60-i3 and antibody JR4 in complex with gp120 define more Cluster A epitopes involved in effective antibody-dependent effector function against HIV-1.” Journal of Virology. (2015) in press.Wang, C., Shen, M., Gohain, N., Tolbert, W. D., Chen, F., Zhang, N., Yang, K., Wang, A., Su, Y., Cheng, T., Zhao, J., Pazgier, M., and Wang, J. “Design of a potent antibiotic peptide based on the active region of human defensing 5.” Journal of Medicinal Chemistry. 7:3083-3093 (2015).Acharya, P., Tolbert, W. D., Gohain, N., Wu, X., Yu, L., Liu, T., Huang, W., Huang, C.-C., Kwon, Y. D., Louder, R. K., Luongo, T. S., McLellan, J. S., Pancera, M., Yang, Y., Zhang, B., Flinko, R., Foulk, Jr., J. S., Sajadi, M. M., Kamin-Lewis, R., Robinson, J. E., Martin, L., Kwong, P. D., Guan, Y. DeVico, A. L., Lewis, G. K., and Pazgier, M. “Structural definition of an antibody-dependent cellular cytotoxicity response implicated in reduced risk for HIV-1 infection.” Journal of Virology. 88: 12895-12906 (2014).Zhao, L., Tolbert, W. D., Ericksen, B., Zhan, C., Wu, X., Yuan, W., Li, X., Pazgier, M., and Lu, W. “Single, double and quadruple alanine substitutions at oligomeric interfaces identify hydrophobicity as the key determinant of human neutrophil alpha defensin HNP1 function.” PLoS ONE. 8(11): e78937 (2013).

Greater Grand Rapids, Michigan Area

Work focused on the hepatocyte growth factor/scatter factor and its receptor the Met tyrosine kinase and on determining structures of glucocorticoid receptor ligand complexes. Engineered an antagonist version of a truncated hepatocyte growth factor/scatter factor through mutagenesis based upon crystal structure information and optimized its expression for potential use as a therapeutic.He, Y., Yi, W., Powell, K., Zhou, X. E., Tolbert, W. D., Tang, X., Yang, J., Yang, H., Shi, J., Hou, L., Jiang, H., Melcher, K., and Xu, H. E. “Structures and mechanism for the design of highly potent glucocorticoids.” Cell Research. 24: 713-726 (2014).Tolbert, W. D., Daugherty-Holtrop, J., Gherardi, E., Vande Woude, G., and Xu, H. E. “Structural basis for agonism and antagonism of hepatocyte growth factor.” Proceedings of the National Academy of Sciences of the United States of America. 107: 13264-13269 (2010).Suino-Powell, K., Xu, Y., Zhang, C., Tao, Y.-G., Tolbert, W. D., Simons, Jr., S. S., and Xu H. E. “Doubling the size of the glucocorticoid receptor ligand binding pocket by deacylcortivazol.” Molecular and Cellular Biology. 28: 1915-1923 (2008).Tolbert, W. D., Daugherty, J., Gao, C.-F., Xie, Q., Miranti, C., Gherardi, E., Vande Woude, G., and Xu, H. E. “A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist.” Proceedings of the National Academy of Sciences of the United States of America. 104: 14592–14597 (2007).

Ithaca, New York Area

Determined the structures of several complexes of S-adenosylmethionine decarboxylase (AdoMetDC) with the goal of understanding its enzymatic function and aiding in the design of novel anticancer and antitrypanosomal drugs. Inhibitors of AdoMetDC like the inhibitors of the other main branchpoint in polyamine biosynthesis, ornithine decarboxylase, have resulted in compounds that are undergoing testing as drugs for a number of human diseases. Structure determination of Methanococcus jannaschii arginine decarboxylase. Tolbert, W. D., Graham, D. E., White, R. H., and Ealick, S. E. “Pyruvoyl-dependent Arginine Decarboxylase from Methanococcus jannaschii: Crystal Structures of the Self-cleaved and S53A Proenzyme Forms.” Structure. 11: 285-294 (2003).Tolbert, W. D., Zhang, Y., Cottet, S. E., Bennett, E. M., Ekstrom, J. L., Pegg, A. E., and Ealick, S. E. “Mechanism of Human S-Adenosylmethionine Decarboxylase Proenzyme Processing as Revealed by the Structure of the S68A Mutant.” Biochemistry. 42: 2386-2395 (2003).Ekstrom, J. L., Tolbert, W. D., Xiong, H., Pegg, A. E., and Ealick, S. E. “Structure of a Human S-Adenosylmethionine Decarboxylase Self-Processing Ester Intermediate and Mechanism of Putrescine Stimulation of Processing As Revealed by the H243A Mutant.” Biochemistry. 40: 9495-9504 (2001).Tolbert, W. D., Ekstrom, J. L., Mathews, I. I., Secrist, III, J. A., Kapoor, P., Pegg, A. E., and Ealick, S. E. “The Structural Basis for Substrate Specificity and Inhibition of Human S-Adenosylmethionine Decarboxylase.” Biochemistry. 40: 9484-9494 (2001).

Lexington, Kentucky Area

Initial fit of the electron density for the structure of rat neurolysin, a 78 kDa zinc dependent protease involved in neuropeptide degradation. The initial model to 3.5 Å from a MAD methyl mercury chloride derivative data set and a selenomethionine derivative data set was later refined to 2.3 Å.Brown, C. K., Madauss, K., Lian, W., Beck, M. R., Tolbert, W. D., and Rodgers, D. W. “Structure of Neurolysin Reveals a Deep Channel that Limits Substrate Access.” Proceedings of the National Academy of Sciences of the United States of America. 98: 3127-3132 (2001).

Charlottesville, Virginia Area

Crystallized and began heavy atom screens of two enzymes, 3-deoxy-D-manno-octulosonate-8-phosphate synthase from Escherichia coli, an enzyme essential for LPS formation in Gram-negative bacteria, and the partial complex of anthranilate synthase from Salmonella typhimurium, the first step in tryptophan biosynthesis. Teaching assistant for Biology 203, Biology 204, and Chemistry 452: introductory biology and biochemistry lab courses.Wagner, T., Kretsinger, R. H., Bauerle, R., and Tolbert, W. D. “3-Deoxy-D-manno-octulosonate-8-phosphate Synthase from Escherichia coli. Model of Binding of Phosphoenolpyruvate and D-arabinose-5-phosphate.” Journal of Molecular Biology. 301: 233-238 (2000).Tolbert, W. D., Chatterji, S., Bauerle, R., and Kretsinger R. “Crystallization and Preliminary Crystallographic Studies of the Anthranilate Synthase Partial Complex from Salmonella typhimurium.” Acta Crystallographica Section D. D55: 305-306 (1999).Tolbert, W. D., Moll, J. R., Bauerle, R., and Kretsinger, R. H. “Crystallization and Preliminary Crystallographic Studies of 3-deoxy-D-manno-octulosonate-8-phosphate Synthase from Escherichia coli.” Proteins: Structure, Function, and Genetics. 24: 407-408 (1996).Kretsinger, R. H., Tolbert, D., Nakayama, S., and Pearson, W. “The EF-Hand, Homologs, and Analogs.” in Novel Calcium Binding Proteins ed. C. Heizmann. Springer Verlag (1991).

Ph.D., Biology

Ms, Biology

Ba, Chemistry