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The Zhang Laboratory


Padayatti PS, Lee SC, Stanfield RL, Wen P-C, Tajkhorshid E, Wilson IA, Zhang Q. Structural Insights into the Lipid A Transport Pathway in MsbA. Structure 2019, 27:1114-1123.

Zhang Q, Cherezov V. Chemical Tools for Membrane Protein Structural Biology. Curr. Opin. Struct. Biol. 2019,

Waghray D, Zhang Q. Inhibit or Evade Multidrug Resistance P-glycoprotein in Cancer Treatment. J. Med. Chem. 2018, 61:5108-5121.

Shah MB, Zhang Q, Halpert JR. Crystal Structural of CYP2B6 in Complex with an Efavirenz Analog. Int. J. Mol. Sci. 2018, 19:1025.

Ishchenko A, Peng L, Zinovev E, Vlasov A, Lee SC, Kuklin A, Mishin A, Borshchevskiy V, Zhang Q, Cherezov V. Chemically Stable Lipids for Membrane Protein Crystallization. Cryst. Growth and Des. 2017, 17:3502-3511.

Zhang Q, Padayatti PS, Leung JH. Proton-translocating Nicotinamide Nucleotide Transhydrogenase: A Structural Perspective. Front. Physiol. 2017, 8:1089.

Maekawa K, Adachi M, Matsuzawa Y, Zhang Q, Kuroki R, Saito Y, Shah M. Structural Basis of Single Nucleotide Polymorphisms in Cytochrome P450 2C9. Biochemistry, 2017, 56:5476-5480.

Padayatti PS, Leung JH, Mahinthichaichan P, Tajkhorshid E, Ishchenko A, Cherezov V, Soltis SM, Jackson JB, Stout CD, Gennis RB, and Zhang Q. Critical Role of Water Molecules in Proton Translocation by the Membrane-bound Transhydrogenase. Structure 2017, 25:1111-9.

Shah MB, Liu J, Zhang Q, Stout CD and Halpert JR. Halogen-p Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity. ACS Chem. Biol. 2017, 12:1204-1210.

Bennett BC, Purdy MD, Baker KA, Achara C, McIntire WE, Stevens RC, Zhang Q, Harris A, Abagyan R, Yeager M. An Electrostatic Mechanism for Ca2+-mediated Regulation of Gap Junction Channels. Nat. Commun. 2016, 7:8770.

Shah MB, Jang H-H, Wilderman PR, Lee D, Li S, Zhang Q, Stout CD, Halpert JR. Effect of Detergent Binding on Cytochrome P450 2B4 Structure as Analyzed by X-ray Crystallography and Deuterium-Exchange Mass Spectrometry. Biophys. Chem. 2016, 216:1-8.

Liu J, Shah MB, Zhang Q, Stout CD, Halpert JR, Wilderman PR. Coumarin Derivatives as Substrate Probes of Mammalian Cytochromes P450 2B4 and 2B6: Assessing the Importance of 7-Alkoxy Chain Length, Halogen Substitution, and Non-Active Site Mutations. Biochemistry 2016, 55:1997-2007.

Shah MB, Huo L, Liu J, Zhang Q, Dearing MD, Wilderman PR, Szklarz G, Stout CD, Halpert JR. Structure-Function Analysis of Mammalian CYP2B Enzymes using 7-Substituted Coumarin Derivatives as Probes: Utility of Crystal Structures and Molecular Modeling in Understanding Xenobiotic Metabolism. Mol. Pharmacol. 2016, 89:435-45.

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.

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.

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.

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.

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.

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. 

Gökirmak T, Campanale JP, Shipp LE, Moy G, Tao H, Hamdoun A, Localization and substrate selectivity of sea urchin multidrug (MDR) efflux transporters. J. Biol. Chem. 2012, 287, 43876-43883.

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. 

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. 

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.

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.

Zhang Q, Tao H, Hong W-X. New Amphiphiles for Membrane Protein Structural Biology. Methods 2011, 55:318-23.

Shah MB, Pascual J, Zhang Q, Stout CD, Halpert JR. Structures of Cytochrome P450 2B6 Bound to 4-Benzylpyridine and 4-(4-Nitrobenzyl)pyridine:  Insight into Inhibitor Binding and Rearrangement of Active Site Side Chains. Mol. Pharmacol. 2011, 80:1047-55.

Gay SC, Zhang H, Wilderman PR, Roberts AG, Liu T, Li S, Lin H, Zhang Q, Woods Jr. VL, Stout CD, Hollenberg PF, Halpert JR. Structural Analysis of Mammalian Cytochrome P450 2B4 Covalently Bound to the Mechanism-Based Inactivator tert-Butylphenylacetylene: Insight into Partial Enzymatic Activity. Biochemistry 2011, 50:4903-11.

Yu F, Weng Y, Hong W-X, Zhang Q. Efficient Synthesis of Unsaturated 1-Monoacyl Glycerols for in meso Crystallization of Membrane Proteins. Synlett 2011, 809-812.

Hou T, Weng Y, Zhuo R, Chang G, Urbatsch IL, Zhang Q. Design and Synthesis of Selenazole-Containing Peptides for Co-crystallization with P-glycoprotein. ChemBioChem 2011, 12:868-73.

Wilderman PR, Shah MB, Liu T, Li S, Hsu, S, Roberts AG, Goodlett DR, Zhang Q, Woods Jr. VL, Stout CD, Halpert JR. Plasticity of Cytochrome P450 2B4 as Investigated by Hydrogen-Deuterium Exchange Mass Spectrometry and X-Ray Crystallography. J. Biol. Chem. 2010, 285:38602-11.

Xiao H, Szewczyk P, Karyakin A, Evin R, Hong W-X, Zhang Q, Chang, G. Structure of a Cation-bound Multidrug and Toxic Compound Extrusion Transporter. Nature 2010, 467:991-4.

Gay SB, Roberts AG, Maekawa, K, Talakad, JC, Hong W-X, Zhang Q, Stout CD, Halpert JR. Cytochrome P450 2B4 Complexed with Antiplatelet Drugs Ticlopidine and Clopidogrel. Biochemistry 2010, 49:8709-20.

Hong W-X, Kent BA, Ma X, Stevens RC, Yeager M, Zhang Q. Design, Synthesis, and Properties of Branch-chained Maltoside Detergents for Stabilization and Crystallization of Integral Membrane Proteins: Human Connexin 26. Langmuir 2010, 26(11):8690-6.

Gay SB, Shah MB, Talakad JC, Maekawa K, Roberts AG, Wilderman PR, Sun L, Yang JY, Huelga SC, Hong W-X, Zhang Q, Stout CD, Halpert JR. Crystal Structure of a Cytochrome P450 2B6 Genetic Variant in Complex with the Inhibitor 4-(4-Chlorophenyl)imidazole at 2.0 Å Resolution. Mol. Pharmacol. 2010, 77:529-38.

Annalora A, Goodin DB, Hong W-X, Zhang Q, Johnson EF, Stout CD. The Crystal Structure of CYP24A1, A Mitochondrial Cytochrome P450 Involved in Vitamin D Metabolism. J. Mol. Biol. 2010, 396:441-451.

Aller SG., Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G. Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding. Science 2009, 323:1718-1722.

Zhang Q, Horst R, Geralt M, Ma X, Finn MG, Stevens RC, Wuthrich K. Microscale NMR Screening of New Detergents for Membrane Protein Structural Biology. J. Am. Chem. Soc. 2008, 130:7357-7363.

Zhang Q, Ma X, Ward A, Hong W-X, Jaakola V-P, Stevens RC, Finn MG, Chang G. Designing Facial Amphiphiles for the Stabilization of Integral Membrane Proteins. Angew. Chem. Int. Ed. 2007, 46:7023-7025.


Stewart CR,* Wilson LM,* Zhang Q,* PhamCLL, Waddington L, Stapleton D, Staples MK, Kelly JW, Howlett GJ. Oxidized Cholesterol Metabolites Found in Human Atherosclerotic Lesions Promote Apolipoprotein Amyloid Fibril Formation, Biochemistry 2007, 46:5552-5561. (* equal contribution)

Bieschke J, Zhang Q, Bosco DA, Lerner RA , Powers ET, Wentworth Jr. P, Kelly JW. Small Molecule Oxidation Products Trigger Disease-Associated Protein Misfolding. Acc. Chem. Res. 2006, 39:611-619.

Bosco DA, Fowler D, Zhang Q, Nieva J, Powers ET, Wentworth Jr. P, Lerner RA, Kelly JW. Elevated Levels of Oxidized Cholesterol Metabolites in Lewy Body Disease Brains Accelerate Alpha-Synuclein Fibrillization. Nat. Chem. Biol. 2006, 2:249-253.

Zhang Q, Kelly JW. Cys-10 Mixed Disulfide Modifications Exacerbate Transthyretin Familial Variant Amyloidogenicity: A Likely Explanation for Variable Clinical Expression of Amyloidosis and the Lack of Pathology in C10S/V30M Transgenic Mice? Biochemistry 2005, 44:9079-9085.

Bieschke J, Zhang Q, Powers ET, Lerner RA, Kelly JW. Oxidative Metabolites Accelerate Alzheimer’s Amyloidogenesis by a Two Step Mechanism, Eliminating the Requirement for Nucleation. Biochemistry 2005, 44:4977-4983.

Zhang Q, Xu W, Lu X. Cycloisomerization of 1,6-Enynes Using Acetate as Nucleophile under Palladium(II) Catalysis. J. Org. Chem. 2005, 70:1505-1507.

Zhang Q, Powers ET, Nieva J, Huff ME, Galve R, Dendle MA, Bieschke J, Glabe CG, Eschenmoser A, Wentworth Jr. P, Lerner RA, Kelly JW. Metabolite Initiated Protein Misfolding May Trigger Alzheimer’s Disease. Proc. Natl. Acad. Sci. USA 2004, 101:4752-4757.

Zhang Q, Kelly, JW. Cys10 Mixed Disulfides Make Transthyretin More Amyloidogenic under Mildly Acidic Conditions. Biochemistry 2003, 42:8756-8761.

Zhang Q, Lu X, Han X. Palladium(II)-Catalyzed Asymmetric Cyclization of (Z)-4'-Acetoxy-2'-butenyl 2-Alkynoates. Role of Nitrogen-Containing Ligands in Palladium(II)-Mediated Reactions. J. Org. Chem. 2001, 66:7676-7684.

Zhang Q, Lu X. Reactions of palladium enolate intermediate with electrophiles under divalent palladium catalysis. Huaxue Xuebao 2001, 59:1702-1706.

Zhang Z, Lu X, Xu Z, Zhang Q, Han, X. Role of Halide Ions in Divalent Palladium-Mediated Reactions: Competition between b-Heteroatom Elimination and b-Hydride Elimination of a Carbon-Palladium Bond. Organometallics 2001, 20:3724-3728.

Lu X, Zhang Q. Effect of ligands on the divalent palladium-catalyzed carbon-carbon coupling reactions. Highly enantioselective synthesis of optically active g-butyrolactones. Pure Appl. Chem. 2001, 73:247-250.

Zhang Q, Lu X. Highly enantioselective palladium(II)-catalyzed cyclization of (Z)-4'-acetoxy-2'-butenyl -2-alkynoates: an efficient synthesis of optically active g-butyrolactones. J. Am. Chem. Soc. 2000, 122:7604-7605.



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