Research InterestsThe research in my laboratory is mainly in the area of protein biochemistry focusing on protein structure, function, and dynamics with applications to protein engineering and structure-based drug design. We study protein biochemistry from both structural and functional perspectives. Thus, a multidisciplinary approach, including molecular genetic, biochemical, bio-organic, biophysical, and computational methods, has been employed in our research. The main structural technique is multidimensional NMR spectroscopy, the most powerful spectroscopic technique that can be used not only to determine the three-dimensional structures of proteins but also to elucidate their chemical and dynamic properties in solution at atomic resolution. The thrust of our research is to understand the relationships between structure, function, and dynamics in enzymes, particularly enzymes in the folate biosynthetic pathway and nucleotide metabolism, because these enzymes are not only good model systems for addressing the important biochemical issues that we are interested in but also of great medical significance. MORE
Shi GB, Shaw G, Li Y, Wu Y, Yan HG, Ji XH. 2012. Bisubstrate analog inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: New lead exhibits a distinct binding mode. Biorganic & Medicinal Chemistry 20 4303-4309.
Wang J, Sklenak S, Liu A, Felczak K, Wu Y, Li Y, Yan H. (2012) Role of glutamate 64 in the activation of the prodrug 5-fluorocytosine by yeast cytosine deaminase. Biochemistry 51(1):475-486.
Shi, G. B., Shaw, G., Liang, Y. H., Subburaman, P., Li, Y., Wu, Y., Yan, H., and Ji, X. (2012) Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: New design with improved properties. Bioorg. Med. Chem. 20, 47-57.
He, Y. F., Li, Y., Mukherjee, S., Wu, Y., Yan, H., and Lu, H. P. (2011) Probing single-molecule enzyme active-site conformational state intermittent coherence. J. Am. Chem. Soc. 133, 14389-14395.
Yan, H. and Ji, X. (2011) Role of protein conformational dynamics in the catalysis by 6-hydroxymethyl-7, 8-dihydropterin pyrophosphokinase. Protein Pept. Lett. 18, 328-335.
Zavodszky MI, Rohatgi A, Van Voorst JR, Yan HG, Kuhn LA. (2009) Scoring ligand similarity in structure-based virtual screening. Journal of Molecular Recognition. 22:280-292.
Ray BD, Scott J, Yan H, Rao BD. (2009) Productive versus unproductive nucleotide binding in yeast guanylate kinase mutants: comparison of R41M with K14M by proton two dimensional transferred NOESY. Biochemistry. 48(24):5532-40.
Krishnamurthy H, Munro K, Yan H, Vieille C. (2009) Dynamics in Thermotoga neapolitana adenylate kinase: N-15 relaxation and hydrogen-deuterium exchange studies of a hyperthermophilic enzyme highly active at 30 degrees C. Biochemistry 48, 2723-2739.
Lescop E, Lu Z, Liu Q, Xu H, Li G, Xia B, Yan H, Jin C. (2009) Dynamics of the conformational transitions in the assembling of the Michaelis Complex of a bisubstrate enzyme: A 15N relaxation study of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. Biochemistry 48 (2), 302-312.
Liu A, Lu Z, Wang J, Yao L, Li Y, Yan H. (2008) NMR detection of bifurcated hydrogen bonds in large proteins. J Am Chem Soc. 130(8):2428-9.
Blaszczyk, J., Li, Y., Gan, J., Yan, H.*, and Ji, X.* (2007) Structural basis and catalytic mechanism for the aldolase and epimerase activities of Staphylococcus aureus dihydroneopterin aldolase. J. Mol. Biol. 368, 161-169.
Blaszczyk, J., Li, Y., Cherry, S., Alexandratos, J., Wu, W., Shaw G., Tropea, J. E., Waugh, D. S., Yan, H.*, and Ji, X.* (2007) Structure and activity of Yersinia pestis 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as a novel target for the development of antiplague therapeutics. Acta Crystallogr. 63 (Pt 11):1169-77.
Gan, J., Wu, Y., Prabakaran, P., Gu, Y., Li, Y., Andrykovitch, M., Liu, H., Gong, Y., Yan, H.*, and Ji, X.* (2007) Structural and biochemical analyses of shikimate dehydrogenase AroE from Aquifex aeolicus: implications for the catalytic mechanism. Biochemistry 46, 9513-9522.
Wang, Y., Li, Y., Wu, Y., and Yan, H. (2007) Mechanism of dihydroneopterin aldolase: NMR, equilibrium and transient kinetic studies of the Staphylococcus aureus and Escherichia coli enzymes. FEBS J. 274, 2240-2252.
Yao, L., Cukier, R. I.*, and Yan, H.* (2007) Catalytic mechanism of guanine deaminase: An ONIOM and molecular dynamics study. J. Phys. Chem. B 111, 4200-4210.
Liu*, A., Yao, L., Li, Y., and Yan, H. (2007) TROSY of side-chain amides in large proteins. J. Magn Reson., in press.
Yao, L., Yan, H.*, and Cukier, R. I.* (2007) A molecular dynamics study of the ligand release path in yeast cytosine deaminase. Biophys. J. 92, 2301-2310. MORE