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
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. PMC3684837
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. PMC3683783
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. PMC3612649
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. PMC3580012
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. PMC3568706
Shah MB, Wilderman PR, Pascual J, Zhang Q, Stout CD, and Halpert JR. Conformational Adaptation of Human Cytochrome P450 2B6 and Rabbit Cytochrome P450 2B4 Revealed Upon Binding Multiple Amlodipine Molecules. Biochemistry 2012, 51:7225-38. PMC3485383
Stanczak P, Zhang Q, Serrano P, Horst R, Wuthrich K. Micro-coil NMR to Optimize Reconstitution Conditions of OmpW in Detergent Micelles. J. Biomol. NMR 2012, 54:129-33.
Tao H, Fu Y, Thompson AA, Lee SC, Mahoney N, Stevens RC, Zhang Q. Synthesis and Properties of Dodecyl Trehaloside Detergents for Membrane Protein Studies. Langmuir 2012, 28:11173-81. PMC 3418823
Jiang X, Guan L, Zhou Y, Hong W-X, Zhang Q, Kaback HR. Evidence for an intermediate conformer of LacY. Proc. Natl. Acad. Sci. USA 2012, 109:E698-704. PMC 3311394.
Wilderman PR, Gay S, Jang H-H, Zhang Q, Stout CD, Halpert JR. Investigation by site-directed mutagenesis of the role of cytochrome P450 2B4 non-active site residues in protein-ligand interactions based on crystal structures of the ligand-bound enzyme. FEBS J. 2012, 279:1607-20.