BS, Biochemistry and Molecular Biology, Peking University, 1997
Research Interests
The Chen lab (http://www.thechenlab.com) focuses on structure-based drug design against proteins involved in infectious diseases and cancer. We utilize a multi-disciplinary approach, combining biochemistry, structural biology and computational chemistry, to investigate the function and inhibition of enzymes related to bacterial cell wall synthesis, the biological process targeted by antibiotics such as penicillin. We also study human signal transduction proteins in collaboration with other laboratories. Our research goals include:
Studying molecular interactions at atomic and ultimately subatomic scale through ultra-high resolution X-ray crystallography;
Developing fragment-based molecular docking for drug discovery;
Identifying novel inhibitors as potential drug leads and chemical probes for proteins of biomedical importance.
Memberships
Member (American Chemical Society, 2009 - Present)
Recent Publications
Pemberton OA, Zhang X, Chen Y. Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2).Journal of medicinal chemistry. 60(8) : 3525-3530, 2017.
Smith EW, Nevins AM, Qiao Z, Liu Y, Getschman AE, Vankayala SL, Kemp MT, Peterson FC, Li R, Volkman BF, Chen Y. Structure-Based Identification of Novel Ligands Targeting Multiple Sites within a Chemokine-G-Protein-Coupled-Receptor Interface.Journal of medicinal chemistry. 59(9) : 4342-51, 2016.
Smith EW, Lewandowski EM, Moussouras NA, Kroeck KG, Volkman BF, Veldkamp CT, Chen Y. Crystallographic Structure of Truncated CCL21 and the Putative Sulfotyrosine-Binding Site.Biochemistry. 55(40) : 5746-5753, 2016.
Lewandowski E, M, Skiba J, Torelli N, J, Rajnisz A, Solecka J, Kowalski K, Chen Y. Antibacterial properties and atomic resolution X-ray complex crystal structure of a ruthenocene conjugated β-lactam antibiotic.Chem. Commun.. 51(28) : 6186-9, 2015.
Smith E, W, Zhang X, Behzadi C, Andrews L, D, Cohen F, Chen Y. Structures of Pseudomonas aeruginosa LpxA reveal basis for substrate selectivity.Biochemistry. (Accepted). , 2015.
Nichols D, A, Hargis J, C, Sanishvili R, Jaishanka P, Defrees K, Smith E, W, Wang K, K, Prati F, Renslo A, R, Woodcock H, L, Chen Y. Ligand-induced proton transfer and low-barrier hydrogen bond revealed by X-ray crystallography.J. Am. Chem. Soc.. 137(25) : 8086-95, 2015.
Smith E, W, Liu Y, Getschman A, E, Peterson F, C, Ziarek J, J, Li R, Volkman B, K, Chen Y. Structural analysis of a novel small molecule ligand bound to the CXCL12 chemokine.J. Med. Chem. 57(22) : 9693-9, 2014.
Nichols D, A, Renslo A, R, Chen Y. Fragment-based inhibitor discovery against β-lactamases.Future Med. Chem. 6(4) : 413-27, 2014.
Jehle K, Cato L, Neeb A, Muhle-Goll C, Jung N, Smith E, W, Buzon V, Carbó L, R, Estébanez-Perpiñá E, Schmitz K, Fruk L, Luy B, Chen Y, Cox M, B, Bräse S, Brown M, Cato A, C. Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-binding Motif.J. Biol. Chem. 289(13) : 8839-51, 2014.
Hargis J, C, White J, K, Chen Y, Woodcock H, L. Can Molecular Dynamics and QM/MM solve the Penicillin Binding Protein Protonation Puzzle?J. Chem. Inf. Mod. 54(5) : 1412-24, 2014.
Smith J, Zhang W, Kumarasiri M, Hesek D, Lee M, Toth M, Vakulenko S, Fisher J, Mobashery S, Chen Y. Kinetic Characterization and Crystal Structure of Penicillin-Binding Protein 5 from Pseudomonas aeruginosa.Antimicrob. Agents Chemother. 57(7) : 3137-46, 2013.
Hung M, S, Xu Z, Chen Y, Smith E, Lin Y, Yang C, Jablons D, M, You L. Hematein, a casein kinase II inhibitor, inhibits lung cancer tumor growth in a murine xenograft model.Int. J. Oncol.. 43(5) : 1517-22, 2013.
Ziarek J, J, Liu Y, Smith E, Zhang G, Peterson F, C, Chen J, Yu Y, Chen Y, Volkman B, F, Li R. Fragment-based optimization of small molecule CXCL12 inhibitors for antagonizing the CXCL12/CXCR4 interaction.Curr Top Med Chem. 12(24) : 2727-40, 2012.
Nichols DA, Jaishankar P, Larson W, Smith E, Liu G, Beyrouthy R, Bonnet R, Renslo AR, Chen Y. Structure-based design of potent and ligand-efficient inhibitors of CTX-M class A β-lactamase.Journal of medicinal chemistry. 55(5) : 2163-72, 2012.
Tomanicek SJ, Wang KK, Weiss KL, Blakeley MP, Cooper J, Chen Y, Coates L. The active site protonation states of perdeuterated Toho-1 beta-lactamase determined by neutron diffraction support a role for Glu166 as the general base in acylation.FEBS letters. 585(2) : 364-8, 2011.
De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Kim YS, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, Neckers LM, Cox MB. Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells.Proceedings of the National Academy of Sciences. 108(29) : 11878-83, 2011.
Chen, Yu|Pohlhaus, Denise Teotico In silico docking and scoring of fragmentsDrug Discovery Today: Technologies. 7(3) : 149-56, 2010.
Tomanicek SJ, Blakeley MP, Cooper J, Chen Y, Afonine PV, Coates L. Neutron diffraction studies of a class A beta-lactamase Toho-1 E166A/R274N/R276N triple mutant.Journal of molecular biology. 396(4) : 1070-80, 2010.
Veldkamp CT, Ziarek JJ, Peterson FC, Chen Y, Volkman BF. Targeting SDF-1/CXCL12 with a ligand that prevents activation of CXCR4 through structure-based drug design.Journal of the American Chemical Society. 132(21) : 7242-3, 2010.
Chen Y, Shoichet BK. Molecular docking and ligand specificity in fragment-based inhibitor discovery.Nature chemical biology. 5(5) : 358-64, 2009.
Chen Y, McReynolds A, Shoichet BK. Re-examining the role of Lys67 in class C beta-lactamase catalysis.Protein Science. 18(3) : 662-9, 2009.
Chen Y, Zhang W, Shi Q, Hesek D, Lee M, Mobashery S, Shoichet BK. Crystal structures of penicillin-binding protein 6 from Escherichia coli.Journal of the American Chemical Society. 131(40) : 14345-54, 2009.
Delmas J, Chen Y, Prati F, Robin F, Shoichet BK, Bonnet R. Structure and dynamics of CTX-M enzymes reveal insights into substrate accommodation by extended-spectrum beta-lactamases.Journal of molecular biology. 375(1) : 192-201, 2008.
Whiteson KL, Chen Y, Chopra N, Raymond AC, Rice PA. Identification of a potential general acid/base in the reversible phosphoryl transfer reactions catalyzed by tyrosine recombinases: Flp H305.Chemistry & biology. 14(2) : 121-9, 2007.
Chen Y, Bonnet R, Shoichet BK. The acylation mechanism of CTX-M beta-lactamase at 0.88 a resolution.Journal of the American Chemical Society. 129(17) : 5378-80, 2007.
Chen Y, Minasov G, Roth TA, Prati F, Shoichet BK. The deacylation mechanism of AmpC beta-lactamase at ultrahigh resolution.Journal of the American Chemical Society. 128(9) : 2970-6, 2006.
Chen Y, Delmas J, Sirot J, Shoichet B, Bonnet R. Atomic resolution structures of CTX-M beta-lactamases: extended spectrum activities from increased mobility and decreased stability.Journal of molecular biology. 348(2) : 349-62, 2005.
Chen Y, Shoichet B, Bonnet R. Structure, function, and inhibition along the reaction coordinate of CTX-M beta-lactamases.Journal of the American Chemical Society. 127(15) : 5423-34, 2005.
Chen Y, Rice PA. New insight into site-specific recombination from Flp recombinase-DNA structures.Annual review of biophysics and biomolecular structure. 32: 135-59, 2003.
Chen Y, Rice PA. The role of the conserved Trp330 in Flp-mediated recombination. Functional and structural analysis.The Journal of biological chemistry. 278(27) : 24800-7, 2003.
Chen Y, Narendra U, Iype LE, Cox MM, Rice PA. Crystal structure of a Flp recombinase-Holliday junction complex: assembly of an active oligomer by helix swapping.Molecular cell. 6(4) : 885-97, 2000.
Positions Held
Post Doctoral Fellow (Pharmaceutical Chemistry, University of California, San Francisco 2003 - 2009)
Post Doctoral Fellow (Biochemistry and Molecular Biology, University of Chicago, 2003 - 2003)
