Weiping Zheng

Research Interests

Protein post-translational modifications (PTMs) have been increasingly regarded, especially in the post-genomic era, as biological approaches that play a significant role in amplifying the genetic information in higher eukaryotic species including humans through conferring extra level of structural and functional modulation onto proteins. Therefore, the identification of the modifying enzymes and the understanding of the mechanism, specificity, and function of PTMs undoubtedly represent a forefront in the post-genomic research arena. These efforts are not only able to unravel fundamental biological mechanisms, but also are critical to developing pharmacological interventions of therapeutic interests. We are employing our research expertise in organic/peptide chemistry, mechanistic enzymology, molecular biology, and protein chemistry to design, synthesize, and characterize bioactive molecules which may serve as molecular probes as well as potential therapeutics. Our current research endeavors are primarily focused on the following two types of PTMs: lysine N(epsilon)-acetylation/deacetylation and lysine N(epsilon)-methylation/demethylation, which are engaged in regulating multiple biological processes such as gene transcription, apoptosis, metabolism, aging, neurodegeneration, and HIV-1 replication.

Selected Publications

1. Hawse, William F.; Hoff, Kevin G.; Fatkins, David G.; Daines, Alison; Zubkova, Olga V.; Schramm, Vern L.; Zheng, Weiping; Wolberger, Cynthia. Structural insights into intermediate steps in the Sir2 deacetylation reaction. Structure 2008, 16, 1368-1377. (Comment in: Sauve, Anthony A. A SIR-tain Acetyl Complex Is Caught by a Sulfur Trap. Structure, 2008, 16, 1289-1292.)
2. Wei, Lanlan; Jamonnak, Nuttara; Choy, Jeremy; Wang, Zhenghe; Zheng, Weiping. Differential binding modes of the bromodomains of CREB-binding protein (CBP) and p300 with acetylated MyoD. Biochemical and Biophysical Research Communications 2008, 368, 279-284.
3. Fatkins, David G.; Zheng, Weiping. Substituting N(epsilon)-thioacetyllysine for N(epsilon)-acetyllysine in peptide substrates as a general approach to inhibiting human NAD⁺-dependent protein deacetylases. International Journal of Molecular Sciences 2008, 9, 1-11.
4. Fatkins, David G.; Zheng, Weiping. A spectrophotometric assay for histone deacetylase 8. Analytical Biochemistry 2008, 372, 82-88.
5. Liu, Qin; Londraville, Richard; Marrs, James A.; Wilson, Amy L.; Mbimba, Thomas; Murakami, T.; Kubota, F.; Zheng, Weiping; Fatkins, David G. Cadherin-6 function in zebrafish retinal development. Developmental Neurobiology 2008, 68, 1107-1122.
6. Zhang, Xiaodong; Guo, Ailan; Yu, Jianshi; Anthony Possemato, Yueting Chen, Zheng, Weiping; Polakiewicz, Roberto D.; Kinzler, Kenneth W.; Vogelstein, Bert; Velculescu, Victor E.; Wang, Zhenghe John. Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T. Proceedings of the National Academy of  Sciences of USA 2007, 104, 4060-4064. 
7. Jamonnak, Nuttara; Fatkins, David G.; Wei, Lanlan; Zheng, Weiping. N(epsilon)-methanesulfonyllysine as a non-hydrolyzable functional surrogate for N(epsilon)-acetyllysine. Organic & Biomolecular Chemistry 2007, 5, 892-896.
8. Fatkins, David G.; Monnot, Andrew D.; Zheng, Weiping. N(epsilon)-thioacetyllysine: a multi-facet functional probe for enzymatic protein lysine N(epsilon)-deacetylation. Bioorganic & Medicinal Chemistry Letters  2006, 16, 3651-3656.
9. Schwarzer, Dirk; Zhang, Zhongsen; Zheng, Weiping; Cole, Philip A. Negative regulation of a protein tyrosine phosphatase by tyrosine phosphorylation. The Journal of the American Chemical Society  2006, 128, 4192-4193.
10. Lewczuk, Bogdan; Zheng, Weiping; Prusik, Magdalena; Cole, Philip A; Przybylska-Gornowicz, Barbara.  N-bromoacetyltryptamine strongly and reversibly inhibits in vitro melatonin secretion from mammalian pinealocytes.  Neuroendocrinology Letters 2005, 26, 581-592.
11. Zheng, Weiping; Schwarzer, Dirk; LeBeau, Aaron; Weller, Joan L.; Klein, David C.; Cole, Philip A. Cellular stability of serotonin N-acetyltransferase conferred by phosphono-difluoromethylene alanine (Pfa) substitution for Ser205, Journal of Biological Chemistry 2005, 280, 10462-10467.