Department Affiliation: Primary: Pharmacology and Molecular Sciences
Degree: Ph.D., Johns Hopkins University
Rank: Professor
Telephone Number: 410-502-2758
Fax Number: 410-955-3023
E-mail address: jstivers@jhmi.edu
Home Page: Stivers
School of Medicine Address: Room 314 Wood Basic Science Building, 725 N. Wolfe Street, Baltimore, MD 21205
Molecular Mechanism and Inhibition of Enzymes Involved in DNA and RNA Metabolism
- Mechanism and Structure of DNA Repair Enzymes
- NMR and Biophysical Studies of Topoisomerase IB
- Chemical and Dynamic Properties of Enzymes Using Heteronuclear NMR
- Structures of Enzymatic and Non-Enzymatic Transition-States
- Rational Design of Inhibitors and Chemical Probes for Protein-DNA Interactions
Our laboratory focuses on the general problem of specific molecular recognition in biological systems. Our work begins with structure, but we are very interested in pushing and extending the measurement envelope so that we obtain a fundamental understanding of the energetics basis for molecular recognition. Accordingly, we use a wide breadth of molecular, genetic and biophysical approaches that together shed light on aspects of molecular recognition that are not apparent from structural studies alone. Our long-range goal is to use this understanding to design novel small molecules that alter biological pathways within a cellular environment. One approach we are developing is the high-throughput synthesis and screening of small molecule libraries directed at important targets in cancer and viral pathogenesis and in acquired immunity.
Representative Publications:
- Parker, J. B., Bianchet, M. A., Krosky, D. J., Friedman, J. I., Amzel, L. M. and Stivers, J. T. Enzymatic Capture of an Extrahelical Thymine in the Search for Uracil in DNA. Nature 449:433-438, 2007. Pub Med Reference
- Seiple, L. A. Cardellina, J. H. Akee, R. and Stivers J. T. Potent Inhibition of Human AP Endonuclease 1 by Arylstibonic Acids. Mol. Pharmacol. 73:669-677, 2008. Pub Med Reference
- Porecha, R. H., and Stivers, J.T. Uracil DNA Glycosylase Uses DNA Hopping and Short-Range Sliding to Trap Extrahelical Uracils. Proc. Natl. Acad. Sci. USA 105:10791-10796, 2008. Pub Med Reference
- Parker, J. B. and Stivers, J.T. Uracil DNA Glycosylase: Revisiting Substrate-Assisted Catalysis by DNA Phosphate Anions. Biochemistry 47:8614-8622, 2008. Pub Med Reference
- McMahon M.A., Siliciano JD, Lai J, Liu JO, Stivers J.T., Siliciano R.F., Kohli R.M. The anti-herpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multi-drug resistance mutation.J Biol Chem. 283:31289-31293, 2008. (accelerated communication) Pub Med Reference
- Huang, H., Stivers, J.T., Greenberg, M.M. Competitive inhibition of uracil DNA glycosylase by a modified nucleotide whose triphosphate is a substrate for DNA polymerase. J. Am. Chem. Soc., 131, 1344-1345, 2009. Pub Med Reference
- Chung, S., Parker, J.B., Bianchet, M., Amzel, L.M. and Stivers, J.T. Impact of linker strain and flexibility in the design of a fragment-based inhibitor. Nature Chem. Bio. 5:407-413. 2009. Pub Med Reference
- Friedman, J.I., Majumdar, A. and Stivers, J.T. Nontarget DNA binding shapes the dynamic landscape for enzymatic recognition of DNA damage. Nucleic Acids Res. 37:3493-3500, 2009. Pub Med Reference
- Kohli, R., Abrams, S., Gajula, K., Maul, R., Gearhart, P., Stivers, J.T. A portable hotspot recognition loop transfers sequence preferences from APOBEC family members to activation-induced cytidine deaminase. J. Biol. Chem. 284:22898-22904, 2009. Pub Med Reference
Other graduate programs in which Dr. Stivers participates:
BCMB Program
Anti-Cancer Drug Development Program
Chemistry-Biology Interface Program (CBI)
Program in Molecular and Computational Biophysics (PMCB)
