Research Overview

My research interests are mainly focused in three areas: 1) Understanding unfolding-mediated protein aggregation and polymerization using the gS-crystallin protein as a tractable model system.  One hydrophobic mutation of this protein, Opj, exhibits a concentration and temperature-dependent protein aggregation.  The progressive nature of Opj in vivo is similar to those mutations commonly detected in age-related cataracts.  2) Elucidating the mechanism of a novel family of nucleotide hydrolases.  RCL is up-graduated by c-Myc oncogene, and proposed to serve as a nucleotide salvage pathway enzyme and/or promote angiogenesis in many tumor cells.  Structural and kinetic studies indicated that RCL shares some similarity with the deoxynucleoside transferases, but more importantly possesses its novelty both in the structure and in its mechanism underlying the enzymatic catalysis. 3) Investigating the protein-nucleic acid and protein-protein interactions critical for gene regulation by the Gfi-1 transcription factor, which is a vital component in hematopoietic process. The six-zinc finger domain of Gfi-1 has been shown to be responsible for these interactions, and mutants within this domain are associated with AML.  In my laboratory, we use nuclear magnetic resonance (NMR) in parallel with multiple biophysical methods to reveal detailed structural and dynamic information of these macromolecules to help providing fundamental insights into their functional mechanism in their related biological processes.

Recent Publications

Bryon Mahler, Kiran Doddapaneni, Ian Kleckner, Chunhua Yuan, Graeme Wistow, and Zhengrong Wu. (2011) “Characterization of a transient unfolding intermediate in a core mutant of gS-crystallin.” J. Mol. Biol., in press.

Soojin Lee, Bryon Mahler, Jodie Toward, Blake Jones, Keith Wyatt, Lijin Dong, Graeme Wistow and Zhengrong Wu. (2010) “A single destabilizing mutation (F9S) promotes concerted unfolding of an entire globular domain in gS-crystallin.” J. Mol. Biol., 399,320-330.

Soojin Lee, Kiran Doddapaneni, Amber Hogue, Laura McGhee, Shari Meyers and Zhengrong Wu.  (2010) “Solution structure of Gfi1 zinc finger domain bound to its consensus DNA.” J. Mol. Biol., 397, 1055-66.

Kiran Doddapaneni, Bryon Mahler, Ryan Pavlovicz, Adam Haushalter, Chunhua Yuan and Zhengrong Wu.  (2009) “Solution Structure of RCL, a Novel 2’-deoxyribonucleoside 5’-monophosphate N-glycosidase. “ J. Mol. Biol., 394, 423-434.

Jose A. Gomez, Weiyon Sun, Vivian Gama, Dagmar Hajkova, Tomoyuki Yoshida, Zhengrong Wu, Masaru Miyagi, John J. Pink, Mark W. Jackson, David Danielpour and Shigemi Matsuyama. (2009) “The C-terminus of interferon gamma receptor beta chain (IFNgR2) has antiapoptotic activity as a Bax inhibitor.” Cancer Biology & Therapy, 8, 1771-1786.

R. Sounier, L. Blanchard, Z. Wu and J. Boisbouvier. (2007) “High accuracy distance measurement between remote methyls in specifically protonated proteins.” J. Am. Chem. Soc., 129, 472-473.

Hongjie Guo, Kaarina Lokko, Yun Zhang, Wen Yi, Zhengrong Wu, Peng George Wang. (2006) “Overexpression and characterization of Wzz of Escherichia coli O86:H2.” Protein Expr. Purif., 48, 49-55.

M. Maderia M, J. Wu, A. Bax, S. Shenoy, B. O'Keefe, V.E. Marquez, and J.J. Barchi. (2005) “Engineering DNA topology with locked nucleosides: A structural study.” Nucleosides, nucleotides & nucleic acids, 24, 687-690.

Alexander Grishaev, Zhengrong Wu, Jill Trewhella and Ad Bax. (2005) “Refinement of Multi-Domain Protein Structures by Combination of Solution Small Angle X-ray Scattering and NMR Data.” J. Am. Chem. Soc., 127, 16621-16628.

Zhengrong Wu, Frank Delaglio, Keith Wyatt, Graeme Wistow and Ad Bax. (2005) “Solution structure of gS-crystallin by molecular fragment replacement NMR.” Prot. Sci., 14, 3101-3114.

Zhengrong Wu, Melissa Maderia, Joseph Barchi, Victor E. Marquez and Ad Bax. (2005) “Changes in DNA-bending induced by restricting nucleoside ring pucker studied by weak alignment NMR spectroscopy.” Proc. Natl. Acad. Sci. U.S.A, 102, 24-28.

Erin O’Neil-Cabello, Zhengrong Wu, David L. Bryce, Edward P. Nikonowicz and Ad Bax. (2004) “Enhanced spectral resolution in RNA HCP spectra for measurement of 3JC2’P and 3JC4’P couplings and 31P chemical shift changes upon weak alignment.”  J. Biomol. NMR, 30, 61-70.

Jerome Boisbouvier, Zhengrong Wu, Akira Ono, Masatsune Kainosho and Ad Bax. (2003) “Rotational Diffusion Tensor of Nucleic Acids from 13C NMR Relaxation.” J. Biomol. NMR, 27, 133-142.

Dana C. Lawrence, Carrie C. Stover, Jennifer Noznitsky, Zhengrong Wu and Michael F. Summers. (2003) “Structure of the Intact Stem and Bulge of HIV-1 Y-RNA Stem Loop SL1.” J. Mol. Biol, 326, 529-542.

Zhengrong Wu, Frank Delaglio, Nico Tjandra, Victor B. Zhurkin and Ad Bax. (2003) “Overall structure and sugar dynamics of a DNA dodecamer rom homo- and heteronuclear dipolar couplings and 31P chemical shift anisotropy.”  J. Biomol. NMR, 26, 297-315.

Zhengrong Wu, Ad Bax. (2002) “Measurement of Longer-Range 1H-1H Dipolar Couplings in Weakly Aligned Proteins.” J. Am. Chem. Soc., 124, 6972-6973.

Zhengrong Wu, Nico Tjandra, Ad Bax. (2001) 31P Chemical Shift Anisotropy as an Aid in Determining Nucleic Acid Structure in Liquid Crystals.”  J. Am. Chem. Soc., 123, 3617-3618.

Zhengrong Wu, Akira Ono, Masatsune Kainosho, Ad Bax. (2001) “H…N hydrogen bond lengths in double stranded DNA from internucleotide dipolar couplings.”  J. Biomol. NMR. 19, 361-365.

Zhengrong Wu, Nico Tjandra, Ad Bax. (2001) “Measurement of 1H3’-31P dipolar couplings in a DNA oligonucleotide by constant-time NOESY difference spectroscopy.”  J. Biomol. NMR. 19, 367-370.

Frank Delaglio, Zhengrong Wu, Ad Bax. (2001) “Measurement of Homonuclear Proton Couplings from 2D COSY Spectra.” J. Magn. Reson., 149, 276-281.

Zhengrong Wu, Ad Bax. (2001) “Measurement of homonuclear residual dipolar couplings based on cross-peak nulling conditions from 2D CT-COSY.”  J. Magn. Reson., 151, 242-252.

Philip E. Johnson, Ryan B. Turner, Zhengrong Wu, Lea Hairston, Jianhui Guo, Judith G. Levin, Michael F. Summers. (2000) “A Mechanism for (+) strand transfer enhancement by the HIV-1 nucleocapsid protein during reverse transcription.” Biochemistry, 39, 9084-9091.

Gaya K. Amarasinghe, Roberto N. De Guzman, Ryan B. Turner, Kalola Chancellor, Zhengrong Wu, Michael F. Summers. (2000) “NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the Y-RNA packaging signal. Implications for genome recognition.” J. Mol. Biol., 301, 491-511.

Ralph M. Pollack, Lora D. Thornburg, Zhengrong Wu, Michael F. Summers. (1999) “Mechanistic Insights from the Three-Dimensional Structure of 3-Oxo-D5-Steroid Isomerase.” Arch. Biochem. Biophys., 370, 9-15.

Roberto N. De Guzman, Zhengrong Wu, Chelsea C. Stalling, Lucia Pappalardo, Philip N. Borer, Michael F. Summers. (1998) “Structure of the HIV-1 Nucleocapsid Protein Bound to the SL3 Y-RNA Recognition Element.” Science, 279, 384-388.

Zhengrong Wu, Soheila Ebrahimian, Michael E. Zawrotny, Lora D. Thornburg, Gabriela C. Perez-Alvarado, Paul Brothers, Ralph M. Pollack, Michael F. Summers. (1997) “Solution Structure of 3-Oxo-D5-Steroid Isomerase.” Science, 276, 415-418.