研究领域

Biochemistry

Generally speaking, my research focuses on understanding important biological phenomena that involve interactions between complex carbohydrates ("sugars") and proteins. Complex carbohydrates form the outer coating of most cells and their interactions with proteins have been increasingly recognized as important modulators in critical events such as cancer cell metastasis, leukocyte activation and stem cell differentiations, just to name a few. My goal is to understand how carbohydrates control these phenomena and how to manipulate these carbohydrate-protein interactions for the benefit of human health. A particular species of carbohydrates I am interested in is a class of sulfated polysaccharides known as glycosaminoglyans (GAGs). These highly charged molecules bind a host of important targets including growth factors, signaling cytokines and numerous enzymes and lectins. They have been implicated in diseases such as cancer, diabetes, thrombosis, Alzheimer's disease and many types of microbial infections. Despite their importance, very little is known about underlying principles controlling their specificity for proteins. My goal is to study the detailed structural interactions between GAGs and their target proteins using various biophysical techniques, with the final aim being the design of GAG mimics that can inhibit specifically GAG-protein interactions. In particular, I want to focus on determining whether carbohydrate type, sulfation configuration as well as dynamics of the protein side chains have any bearing on the specificity of GAG-protein interactions. My laboratory uses may analytical and biophysical techniques, but the main technique is solution NMR spectroscopy. NMR is a powerful, versatile tool that can be used to probe many systems. I am interested in developing novel NMR techniques to study GAG-protein interactions, especially techniques capable of detecting intermolecular electrostatic interactions. I am also interested in improving present methodologies for purifying structurally homogeneous GAG oligomers through chemical and enzymatic derivatizations as well as producing GAG oligomers labeled with fluorescent, paramagnetic and isotopic tags for use in traditional as well as high-through put investigations.

近期论文

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"RDC-assisted modeling of symmetric protein homo-oligomers," Wang, X., Bansal, S., Jiang, M., Prestegard, J.H. , Prot. Sci 17 899-975 (2008) "Tryptophan Mutants of Cardiac Troponin C: 3D Structure, Troponin I Affinity, and in situ Activity," Julien, O.; Sun, Y.-B.; Wang, X., Biochem 47 597-606 (2008) "Solution structure of Alg13: the sugar donor subunit of a yeast N-acetylglucosamine transferase," 12. Wang, X., Weldeghiorghis, T., Zhang, G., Imeriali, B & Prestegard, J.H, Structure 16 965-975 (2008) "PF0610, a novel winged helix-turn-helix variant possessing a rubredoxin-like Zn ribbon motif from the hyperthermophilic archaeon, Pyrococcus furiosus," Wang, X., Lee, H.-S., Sugar, F. J., Jenney, F. E., Adams, M. W. W., Prestegard, J. H. , Biochemistry 46 752-76 (2007) "Domain-domain motions in proteins from time-modulated pseudocontact shifts," Wang, X., Srisailam, S., Yee, A. A., Lemak, A., Arrowsmith, C., Prestegard, J. H., Tian, F. , J. BioNMR 39 53-61 (2007) "Effects of Phe-to-Trp Mutation & Fluorotryptophan Incorporation on the Solution Structure of Cardiac Troponin C, and Analysis of its Suitability as a Potential Probe for in situ NMR Studies. ," Wang, X., Mercier, P., Letourneau, P. J. & Sykes, B. D., Prot. Sci. 14 2447-2460 (2005) "Structural based insights into the role of troponin in cardiac muscle pathophysiology," Li, M. X. Wang, X. & Sykes, B. D. , J. Muscle Res. Cell Motil. 25 559-79 (2004) "Phosphorylation and mutation of human cardiac troponin I deferentially destabilize the interaction of the functional regions of troponin I with troponin C.," Li, M. X., Wang, X., Lindhout, D. A., Buscemi, N., Van Eyk, J. E. & Sykes, B. D., Biochemistry 42 14460-14468 (2003) "Molecular dissection of the S-adenosylmethionine-binding site of phosphatidylethanolamine N-methyltransferase," Shields, D. J., Altarejos, J. Y., Wang, X., Agellon, L. B. & Vance, D. E. , Journal of Biological Chemistry 278 35826-35836 (2003) "Kinetic studies of calcium and cardiac troponin I peptide binding to human cardiac troponin C using NMR spectroscopy," Li, M. X., Saude, E. J., Wang, X., Pearlstone, J. R., Smillie, L. B. & Sykes, B. D. , European Biophysics Journal with Biophysics Letters 31 245-256 (2002) "Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil.," Wang, X., Li, M. X. & Sykes, B. D. , Journal of Biological Chemistry 277 31124-31133 (2002) "Structure of the C-domain of human cardiac troponin C in complex with the Ca2+ sensitizing drug EMD 57033," Wang, X., Li, M. X., Spyracopoulos, L., Beier, N., Chandra, M., Solaro, R. J. & Sykes, B. D., . Journal of Biological Chemistry 276 , 25456-25466. (2001)