Membrane proteins account for about one third of human genes and comprise more than 50% of human drug targets. Our laboratory is currently focusing on the development of innovative methodologies and chemical tools enabling the structural and functional characterization of membrane proteins. We engage in a number of collaborative projects with experts in membrane protein structural biology to solve biologically significant structures. A second major interest of our laboratory is to study the interactions between membrane proteins and lipids that govern the protein stability and function. We are also interested in the development and discovery of small molecule therapeutics targeting a class of transporters to overcome multidrug resistance in cancer and infectious disease. Developing synthetic methodologies to make biologically relevant molecules is another component of our laboratory.
Ph.D., Organic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 2001
Szewczyk P, Tao H, McGrath AP, Villaluz M, Rees SD, Lee SC, Doshi R, Urbatsch IL, Zhang Q, Chang G. Structural Snapshots of Ligand Entry, Malleable Binding, and Induced Helical Movement in P-glycoprotein. Acta Crystallogr. D Biol. Crystallogr. 2015, 71:732-41.
Moeller A, Lee SC, Tao H, Speir J, Chang G, Urbatsch IL, Potter CS, Carragher B, Zhang Q. Distinct Conformational Spectrum of Homologous Multidrug ABC Transporters. Structure 2015, 23:450-60.
Shah MB, Wilderman PR, Liu J, Jang H-H, Zhang Q, Stout CD, Halpert JR. Structural and Biophysical Characterization of Human Cytochromes P450 2B6 and 2A6 Bound to Volatile Hydrocarbons: Analysis and Comparison. Mol Pharmacol. 2015, 87:649-59.
Peng L, Mo F, Zhang Q. Cholate-based Synthesis of Size-tunable Cage Compounds. J. Org. Chem. 2015, 80:1221-8.
Wang A, Stout CD, Zhang Q, Johnson EF. Contributions of Ionic Interactions and Protein Dynamics to Cytochrome P450 2D6 (CYP2D6) Substrate and Inhibitor Binding. J. Biol. Chem. 2015, 290:5092-14.
Hildebrandt E, Zhang Q, Cant N, Ding H, Dai Q, Peng L, Fu Y, Delucas LJ, Ford R, Kappes JC, Urbatsch IL. A Survey of Detergents for the Purification of Stable, Active Human Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). BBA – Biomembranes. 2014, 1838:2825-37.
Martinez L, Arnaud O, Henin E, Tao H, Chaptal V, Doshi R, Andrieu T, Dussurgey S, Tod M, Di Pietro A, Zhang Q, Chang G, Falson P. Understanding Polyspecificity within the Substrate-binding Cavity of the Human Multidrug Resistance P-glycoprotein. FEBS J. 2014, 281:673-82.
Tao H, Peng L, Zhang Q. Synthesis of Azole-Enriched Cyclopeptides by A Purification Free, Solid Phase-Based Cyclitive Cleavage Strategy. ACS Comb. Sci. 2013, 15:447-51.
Shah MB, Kufareva I, Pascual J, Zhang Q, Stout CD, Halpert JR. A Structural Snapshot of Cytochrome P450 2B4 in Complex with Paroxetine Provides Insights into Ligand Binding and Clusters of Conformational States. J. Pharmacol. Exp. Ther. 2013, 346:113-20.
Tao H, Lee SC, Moeller A, Roy RS, Siu FY, Zimmermann J, Stevens RC, Potter CS, Carragher B, Zhang Q. Engineered Nanostructured b-Sheet Peptides Protect Membrane Proteins. Nat. Methods 2013, 10:759-61.
Marcoux J, Wang S, Politis A, Reading E, Ma J, Biggin P, Zhou M, Tao H, Zhang Q, Chang G, Morgner N, Robinson CV. Mass Spectrometry Reveals Synergistic Effects of Nucleotides, Lipids and Drugs Binding to A Multidrug Resistance Efflux Pump. Proc. Natl. Acad. Sci. USA 2013, 110:9704-9.
Lee SC, Bennett BC, Hong W-X, Fu Y, Baker KA, Marcoux J, Robinson CV, Ward AB, Halpert JR, Stevens RC, Stout CD, Yeager Y, Zhang Q. Steroid-Based Facial Amphiphiles for Stabilization and Crystallization of Membrane Proteins. Proc. Natl. Acad. Sci. USA 2013, 110:E12-3-11.
Shah M, Jang HH, Zhang Q, Stout CD, Halpert JR. X-ray Crystal Structure of the Cytochrome P450 2B4 Active Site Mutant F297A in Complex with Clopidogrel: Insights into Compensatory Rearrangements of the Binding Pocket. Arch. Biochem. Biophys. 2013, 530:64-72.
Zhang H, Gay SC, Shah M, Foroozesh M, Liu J, Osawa Y, Zhang Q, Stout CD, Halpert JR, Hollenberg PF. Potent Mechanism-Based Inactivation Of Cytochrome P450 2B4 By 9-Ethynylphenanthrene: Implications For Allosteric Modulation Of Cytochrome P450 Catalysis. Biochemistry 2013, 52:355-64.