UTMB Center for Addiction Research

David Gorenstein, Ph.D.

Professor

Charles Marc Pomerat Distinguished Professor of Biological Sciences
Associate Dean of Research, School of Medicine

Affiliations: Department of Human Biological Chemistry & Genetics; Sealy Center for Structural Biology; Department of Physiology and Biophysics

Phone: (409) 747-6800
Fax: (409) 747-6850
Email: david@nmr.utmb.edu

Education

• S.B. 1966 Massachusetts Institute of Technology
• A.M. 1967 Harvard University
• Ph.D. 1969 Harvard University

research interests

Our work may be roughly divided into three main areas of structural biology research: (1) development and applications of NMR spectroscopy to biological systems, (2) computational biochemistry, and (3) biomolecular design.

We have been interested in the development of biophysical and bioanalytical applications of NMR spectroscopy to probe the detailed chemical structure and dynamics of biological molecules. Multinuclear NMR of enzyme complexes, nucleic acids, nucleic acid-drug and carcinogen complexes, and nucleic acid protein complexes is being pursued. The laboratory is involved in new instrumentation and computer software development (including further development of a complete relaxation matrix program, MORASS). The laboratory includes state-of-the-art 400 MHz, 600 MHz and 750 MHz NMR spectrometers.

We are studying the detailed solution structure and dynamics of various DNA binding proteins, such as lac repressor headpiece, 434 repressor (both helix turn helix proteins) and NF-IL6 (a basic leucine zipper). Triple resonance, multidimensional NMR is currently being carried out on these and various site-specific mutants with oligonucleotide duplexes. We are also using NMR and molecular dynamics calculations to define the structure and dynamics of other DNA and RNA binding proteins and their oligonucleotide complexes. This includes the HIV-1 nucleocapsid (NCp7), HIV-1 RNAse H and human beta-polymerase.

We also have a major program oriented toward the combinatorial selection, rational design, synthesis and structural characterization of oligonucleotide analogues (especially dithiophosphate analogues) and other agents directed toward the AIDS virus and oncogenes (this includes antisense and aptamer oligonucleotides).

Selected Publications

Joe l Morrisett, Wesley Vick, Rakesh Sharma, Gerald Lawrie, Hazim Safi, Michael Reardon, Edward Ezell, Joseph Schwartz, Glen Hunter, David Gorenstein, “Discrimination of Components in Atherosclerotic Plaques from Human Carotid Endarterectomy Specimens By Magnetic Resonance Imaging Ex Vivo” Magnetic Resonance Imaging, 21, 465-474 (2003).

Yang, X-B., Li, X., Prow, T. W., Reece, L. M., Bassett, S. E., Luxon, B.A., Herzog, N. A., Aronson, Shope, R. E., T. W., Leary, J. F., and Gorenstein, D. G., “Immunofluorescence assay and flow-cytometry selection of bead-bound aptamers”, Nucleic Acids Research, 31, e54 (2003).

V. Thiviyanathan, Y. Yang, K.Kaluarachchi, V. R.. E. Rynbrand, D. G. Gorenstein and S. M. Lemon “High Resolution Structure of a Picornaviral Internal cis -Acting Replication Element ( cre )”, Proc. Natl. Acad. Sci., U.S.A., 101, 12688-12693 (2004).

S. E. Bassett, S. M. Fennewald, D. J. King, Xin Li, N. K. Herzog, R. Shope, Judy F. Aronson, B. A. Luxon, D. G. Gorenstein, “Combinatorial Selection and Edited Combinatorial Selection of Phosphorothioate Aptamers Targeting Human NF- k B RelA /p50 and RelA /RelA” Biochemistry, 43, 9105-9115 (2004).

Raj Kumar, David E. Volk, Jianquan Li, James C. Lee, David G. Gorenstein, and E. Brad Thompson, “TATA-Box Binding Protein Induces Structure in the Recombinant Glucocorticoid Receptor AF1 Domain” Proc. Natl. Acad. Sci., U.S.A., 2004, 101, 16425-16430.

D.E. Volk, D.A. Kallick, M.R. Holbrook, D.W.C. Beasley, A.D.T. Barrett and D.G. Gorenstein, "Solution Structure of Domain III from the Envelope Protein of West Nile Virus strain 385-99", J. Biol. Chem, 279, 38755-38761 (2004).