A microscopic view of the mechanisms of active transport across the cellular membrane

Annual Reports in Computational Chemistry

Volumn 10, Issue , 2014, Pages 77-125

  Enkavi, Giray ^a   Li, Jing ^a   Wen, Pochao ^a   Thangapandian, Sundarapandian ^a   Moradi, Mahmoud ^a   Jiang, Tao ^a   Han, Wei ^a   Tajkhorshid, Emad ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

Conformational changes; Membrane transporters; Molecular dynamics; Nonequilibrium simulation; Primary transporters; Secondary transporters; Substrate binding

Indexed keywords

EID: 84919386963     PISSN: 15741400     EISSN: 18755232     Source Type: Book Series    
DOI: 10.1016/B978-0-444-63378-1.00004-5     Document Type: Chapter

References (208)

1. Nelson D.L., Cox M.M. Lehninger Principles of Biochemistry 2000, Worth Publishers, New York. 3rd ed.
2. Kroetz D.L., Yee S.W., Giacomini K.M. The Pharmacogenomics of Membrane Transporters Project: Research at the Interface of Genomics and Transporter Pharmacology. Clin. Pharmacol. Ther. 2010, 87:109-116.
3. Jardetzky O. Simple Allosteric Model for Membrane Pumps. Nature 1966, 211(5052):969-970.
4. Krishnamurthy H., Piscitelli C.L., Gouaux E. Unlocking the Molecular Secrets of Sodium-Coupled Transporters. Nature 2009, 459:347-355.
5. Locher K.P. Structure and Mechanism of ATP-Binding Cassette Transporters. Philos. Trans. R. Soc. Lond. B 2009, 364(1514):239-245.
6. Boudker O., Verdon G. Structural Perspectives on Secondary Active Transporters. Trends Pharmacol. Sci. 2010, 31:418-426.
7. Forrest L.R., Krämer R., Ziegler C. The Structural Basis of Secondary Active Transport Mechanisms. Biochim. Biophys. Acta 2011, 1807(2):167-188.
8. - Dependent Neurotransmitter Transporters. Nature 2005, 437:215-233.
9. Krishnamurthy H., Gouaux E. X-Ray Structures of LeuT in Substrate-Free Outward-Open and apo Inward-Open States. Nature 2012, 481:469-474.
10. Weyand S., Shimamura T., Yajima S., Suzuki S., Mirza O., Krusong K., Carpenter E.P., Rutherford N.G., Hadden J.M., O'Reilly J., Ma P., Saidijam M., Patching S.G., Hope R.J., Norbertczak H.T., Roach P.C.J., Iwata S., Henderson P.J.F., Cameron A.D. Structure and Molecular Mechanism of a Nucleobase-Cation-Symport-1 Family Transporter. Science 2008, 322:709-713.
11. Shimamura T., Weyand S., Beckstein O., Rutherford N.G., Hadden J.M., Sharples D., Sansom M.S.P., Iwata S., Henderson P.J.F., Cameron A.D. Molecular Basis of Alternating Access Membrane Transport by the Sodium-Hydantoin Transporter Mhp1. Science 2010, 328(5977):470-473.
12. Oldham M.L., Khare D., Quiocho F.A., Davidson A.L., Chen J. Crystal Structure of a Catalytic Intermediate of the Maltose Transporter. Nature 2007, 450(7169):515-521.
13. Khare D., Oldham M.L., Orelle C., Davidson A.L., Chen J. Alternating Access in Maltose Transporter Mediated by Rigid-Body Rotations. Mol. Cell 2009, 33(4):528-536.
14. Oldham M.L., Chen J. Crystal Structure of the Maltose Transporter in a Pretranslocation Intermediate State. Science 2011, 332(6034):1202-1205.
15. Oldham M.L., Chen J. Snapshots of the Maltose Transporter During ATP Hydrolysis. Proc. Natl. Acad. Sci. U. S. A. 2011, 108(37):15152-15156.
16. Yernool D., Boudker O., Jin Y., Gouaux E. Structure of a Glutamate Transporter Homologue from Pyrococcus horikoshii. Nature 2004, 431:811-818.
17. Boudker O., Ryan R.M., Yernool D., Shimamoto K., Gouaux E. Coupling Substrate and Ion Binding to Extracellular Gate of a Sodium-Dependent Aspartate Transporter. Nature 2007, 445:387-393.
18. Reyes N., Ginter C., Boudker O. Transport Mechanism of a Bacterial Homologue of Glutamate Transporters. Nature 2009, 462:880-885.
19. Verdon G., Boudker O. Crystal Structure of an Asymmetric Trimer of a Bacterial Glutamate Transporter Homolog. Nat. Struct. Mol. Biol. 2012, 19:355-357.
20. Vandivort K., Phillips J.C., Villa E., Freddolino P.L., Gumbart J., Trabuco L.G., Chandler D.E., Hsin J., Harrison C.B., Kale L., Schulten K. Long Time and Large Size Molecular Dynamics Simulations Made Feasible Through New TeraGrid Hardware and Software 2008.
21. Dror R.O., Jensen M.O., Borhani D.W., Shaw D.E. Exploring Atomic Resolution Physiology on a Femtosecond to Millisecond Timescale Using Molecular Dynamics Simulations. J. Gen. Physiol. 2010, 135:555-562.
22. Schlick T., Collepardo-Guevara R., Halvorsen L.A., Jung S., Xiao X. Biomolecular Modeling and Simulation: A Field Coming of Age. Q. Rev. Biophys. 2011, 44:191-228.
23. Klauda J.B., Venable R.M., Freites J.A., O'Connor J.W., Tobias D.J., Mondragon-Ramirez C., Vorobyov I., MacKerell A.D., Pastor R.W. Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types. J. Phys. Chem. B 2010, 114(23):7830-7843.
24. + and Substrate Is Triggered by Substrate in a Second Binding Site. Mol. Cell 2008, 30(6):667-677.
25. + Binding Sites with Two Different Mechanisms. J. Mol. Biol. 2008, 377:804-818.
26. Shrivastava I.H., Jiang J., Amara S.G., Bahar I. Time-Resolved Mechanism of Extracellular Gate Opening and Substrate Binding in a Glutamate Transporter. J. Biol. Chem. 2008, 283:28680-28690.
27. D'rozario R.S.G., Sansom M.S.P. Helix Dynamics in a Membrane Transport Protein: Comparative Simulations of the Glycerol-3-Phosphate Transporter and Its Constituent Helices. Mol. Membr. Biol. 2008, 25:571-573.
28. Wang Y., Ohkubo Y.Z., Tajkhorshid E. Gas Conduction of Lipid Bilayers and Membrane Channels. Current Topics in Membranes: Computational Modeling of Membrane Bilayers 2008, Vol. 60:343-367. Elsevier. S. Feller (Ed.).
29. Wen P.-C., Tajkhorshid E. Dimer Opening of the Nucleotide Binding Domains of ABC Transporters After ATP Hydrolysis. Biophys. J. 2008, 95(11):5100-5110.
30. Celik L., Schiott B., Tajkhorshid E. Substrate Binding and Formation of an Occluded State in the Leucine Transporter. Biophys. J. 2008, 94:1600-1612.
31. Huang Z., Tajkhorshid E. Dynamics of the Extracellular Gate and Ion-Substrate Coupling in the Glutamate Transporter. Biophys. J. 2008, 95:2292-2300.
32. Law C.J., Enkavi G., Wang D.-N., Tajkhorshid E. Structural Basis of Substrate Selectivity in the Glycerol-3-Phosphate: Phosphate Antiporter GlpT. Biophys. J. 2009, 97:1346-1353.
33. Gumbart J., Wiener M.C., Tajkhorshid E. Coupling of Calcium and Substrate Binding Through Loop Alignment in the Outer Membrane Transporter BtuB. J. Mol. Biol. 2009, 393:1129-1142.
34. Li J., Tajkhorshid E. Ion-Releasing State of a Secondary Membrane Transporter. Biophys. J. 2009, 97:L29-L31.
35. Zomot E., Bahar I. The Sodium/Galactose Symporter Crystal Structure Is a Dynamic, Not so Occluded State. Mol. BioSyst. 2010, 6:1040-1046.
36. Watanabe A., Choe S., Chaptal V., Rosenberg J.M., Wright E.M., Grabe M., Abramson J. The Mechanism of Sodium and Substrate Release from the Binding Pocket of vSGLT. Nature 2010, 468:988-991.
37. Aittoniemi J., de Wet H., Ashcroft F.M., Sansom M.S.P. Asymmetric Switching in a Homodimeric ABC Transporter: A Simulation Study. PLoS Comput. Biol. 2010, 6(4):e1000762.
38. + Site and the Sequence of Extracellular Binding Events in the Glutamate Transporter. Biophys. J. 2010, 99:1416-1425.
39. Enkavi G., Tajkhorshid E. Simulation of Spontaneous Substrate Binding Revealing the Binding Pathway and Mechanism and Initial Conformational Response of GlpT. Biochemistry 2010, 49:1105-1114.
40. - Dependent Neurotransmitter Transporter Homologue. PLoS Comput. Biol. 2010, 6(8):e1000905.
41. Wen P.-C., Tajkhorshid E. Conformational Coupling of the Nucleotide-Binding and the Transmembrane Domains in the Maltose ABC Transporter. Biophys. J. 2011, 101(3):680-690.
42. +-Galactose Transporter. Biochim. Biophys. Acta 2012, 1818:263-271.
43. Zhao C., Noskov S. The Role of Local Hydration and Hydrogen-Bonding Dynamics in Ion and Solute Release from Ion-Coupled Secondary Transporters. Biochemistry 2011, 50:1848-1856.
44. ph: Insights from Simulations. Mol. BioSyst. 2011, 7:832-842.
45. Gyimesi G., Ramachandran S., Kota P., Dokholyan N.V., Sarkadi B., Hegedüs T. ATP Hydrolysis at One of the Two Sites in ABC Transporters Initiates Transport Related Conformational Transitions. Biochim. Biophys. Acta 2011, 1808(12):2954-2964.
46. Zomot E., Bahar I. Protonation of Glutamate 208 Induces the Release of Agmatine in an Outward-Facing Conformation of an Arginine/Agmatine Antiporter. J. Biol. Chem. 2011, 286:19693-19701.
47. Zomot E., Bahar I. A Conformational Switch in a Partially Unwound Helix Selectively Determines the Pathway for Substrate Release from the Carnitine/γ-Butyrobetaine Antiporter CaiT. J. Biol. Chem. 2012, 287:31823-31832.
48. Wen P.-C., Huang Z., Enkavi G., Wang Y., Gumbart J., Tajkhorshid E. Molecular Mechanisms of Active Transport Across the Cellular Membrane. Molecular Simulations and Biomembranes: From Biophysics to Function 2010, 248-286. Royal Society of Chemistry. P. Biggin, M. Sansom (Eds.).
49. Johnston J.M., Filizola M. Showcasing Modern Molecular Dynamics Simulations of Membrane Proteins Through G Protein-Coupled Receptors. Curr. Opin. Struct. Biol. 2011, 21:552-558.
50. 2+-ATPase. Biophys. J. 2012, 102:268-277.
51. + Binding Sites in Acid Sensing Ion Channel-1. Biophys. J. 2008, 95:5153-5164.
52. Khalili-Araghi F., Gumbart J., Wen P.-C., Sotomayor M., Tajkhorshid E., Schulten K. Molecular Dynamics Simulations of Membrane Channels and Transporters. Curr. Opin. Struct. Biol. 2009, 19:128-137.
53. Wang Y., Shaikh S.A., Tajkhorshid E. Exploring Transmembrane Diffusion Pathways with Molecular Dynamics. Physiology 2010, 25:142-154.
54. Shaikh S.A., Wen P.-C., Enkavi G., Huang Z., Tajkhorshid E. Capturing Functional Motions of Membrane Channels and Transporters with Molecular Dynamics Simulation. J. Comput. Theor. Nanosci. 2010, 7:2481-2500.
55. Huang Z.J., Shaikh S.A., Wen P.-C., Enkavi G., Li J., Tajkhorshid E. Membrane Transporters-Molecular Machines Coupling Cellular Energy to Vectorial Transport Across the Membrane 2011, World Scientific, Singapore.
56. Shaikh S.A., Li J., Enkavi G., Wen P.-C., Huang Z., Tajkhorshid E. Visualizing Functional Motions of Membrane Transporters with Molecular Dynamics Simulations. Biochemistry (Current Topic) 2013, 52:569-587. PMCID: PMC3560430.
57. Allen M.P., Tildesley D.J. Computer Simulation of Liquids 1987, Oxford University Press, New York.
58. Frenkel D., Smit B. Understanding Molecular Simulation from Algorithms to Applications 2002, Academic Press, California.
59. Shaw D.E., Dror R.O., Salmon J.K., Grossman J.P., Mackenzie K.M., Bank J.A., Young C., Deneroff M.M., Batson B., Bowers K.J., Chow E., Eastwood M.P., Ierardi D.J., Klepeis J.L., Kuskin J.S., Larson R.H., Lindorff-Larsen K., Maragakis P., Moraes M.A., Piana S., Shan Y., Towles B. Millisecond-Scale Molecular Dynamics Simulations on Anton 2009, 39:1-39:11. ACM, New York, USA.
60. Lindahl E., Sansom M.S.P. Membrane Proteins: Molecular Dynamics Simulations. Curr. Opin. Struct. Biol. 2008, 18:425-431.
61. Klepeis J.L., Lindorff-Larsen K., Dror R.O., Shaw D.E. Long-Timescale Molecular Dynamics Simulations of Protein Structure and Function. Curr. Opin. Struct. Biol. 2009, 19:120-127.
62. 6-85. J. Am. Chem. Soc. 2011, 133:664-667.
63. Lindorff-Larsen K., Piana S., Dror R.O., Shaw D.E. How Fast-Folding Proteins Fold. Science 2011, 334:517-520.
64. Jensen M.O., Jogini V., Borhani D.W., Leffler A.E., Dror R.O., Shaw D.E. Mechanism of Voltage Gating in Potassium Channels. Science 2012, 336:229-233.
65. Bernstein F.C., Koetzle T.F., Williams G.J., Meyer E.F., Brice M.D., Rogers J.R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: A Computer-Based Archival File for Macromolecular Structures. J. Mol. Biol. 1977, 112(3):535-542.
66. MacKerell A.D., Feig M., Brooks C.L. Extending the Treatment of Backbone Energetics in Protein Force Fields: Limitations of Gas-Phase Quantum Mechanics in Reproducing Protein Conformational Distributions in Molecular Dynamics Simulations. J. Comput. Chem. 2004, 25(11):1400-1415.
67. Mayne C.G., Saam J., Schulten K., Tajkhorshid E., Gumbart J.C. Rapid Parameterization of Small Molecules Using the Force Field Toolkit. J. Comput. Chem. 2013, 34:2757-2770.
68. Roux B. The Calculation of the Potential of Mean Force Using Computer Simulations. Comput. Phys. Commun. 1995, 91:275-282.
69. Barducci A., Bussi G., Parrinello M. Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy Method. Phys. Rev. Lett. 2008, 100:020603.
70. Isralewitz B., Gao M., Schulten K. Steered Molecular Dynamics and Mechanical Functions of Proteins. Curr. Opin. Struct. Biol. 2001, 11:224-230.
71. Schlitter J., Engels M., Krüger P., Jacoby E., Wollmer A. Targeted Molecular Dynamics Simulation of Conformational Change-Application to the T↔R Transition in Insulin. Mol. Simul. 1993, 10(2-6):291-308.
72. Hénin J., Chipot C. Overcoming Free Energy Barriers Using Unconstrained Molecular Dynamics Simulations. J. Chem. Phys. 2004, 121(7):2904-2914.
73. Wang Y., Harrison C.B., Schulten K., McCammon J.A. Implementation of Accelerated Molecular Dynamics in NAMD. Comput. Sci. Discov. 2011, 4. 015002 (11 pages).
74. Moradi M., Tajkhorshid E. Mechanistic Picture for Conformational Transition of a Membrane Transporter at Atomic Resolution. Proc. Natl. Acad. Sci. U. S. A. 2013, 110(47):18916-18921.
75. Moradi M., Tajkhorshid E. Driven Metadynamics: Reconstructing Equilibrium Free Energies from Driven Adaptive-Bias Simulations. J. Phys. Chem. Lett. 2013, 4:1882-1887.
76. Izrailev S., Stepaniants S., Isralewitz B., Kosztin D., Lu H., Molnar F., Wriggers W., Schulten K. Steered Molecular Dynamics. Lecture Notes in Computational Science and Engineering 1998, Vol. 4:39-65. Springer-Verlag, Berlin. P. Deuflhard, J. Hermans, B. Leimkuhler, A.E. Mark, S. Reich, R.D. Skeel (Eds.).
77. Coutsias E.A., Seok C., Dill K.A. Using Quaternions to Calculate RMSD. J. Chem. Phys. 2004, 25(15):1849-1857.
78. Horn B.K.P. Closed-Form Solution of Absolute Orientation Using Unit Quaternions. J. Opt. Soc. Am. A 1987, 4(4):629-642.
79. Halperin I., Ma B., Wolfson H., Nussinov R. Principles of Docking: An Overview of Search Algorithms and a Guide to Scoring Functions. Proteins 2002, 47(4):409-443.
80. B-Rao C., Subramanian J., Sharma S.D. Managing Protein Flexibility in Docking and Its Applications. Drug Discov. Today 2009, 14(7-8):394-400.
81. May A., Zacharias M. Accounting for Global Protein Deformability During Protein-Protein and Protein-Ligand Docking. Biochim. Biophys. Acta 2005, 1754(1-2):225-231.
82. Mihasan M. What In Silico Molecular Docking Can Do for the 'Bench-Working Biologists'. J. Biosci. 2012, 37(6):1089-1095.
83. Lemieux M.J., Huang Y., Wang D.-N. Crystal Structure and Mechanism of GlpT, the Glycerol-3-Phosphate Transporter from E. coli. J. Electron Microsc. 2005, 54:i43-i46.
84. Henderson P.J., Roberts P.E., Martin G.E., Seamon K.B., Walmsley A.R., Rutherford N.G., Varela M.F., Griffith J.K. Homologous Sugar-Transport Proteins in Microbes and Man. Biochem. Soc. Trans. 1993, 21:1002-1006.
85. Paulsen I.T., Nguygn L., Sliwinski M.K., Rabus R., Saier M.H. Microbial Genome Analyses: Comparative Transport Capabilities in Eighteen Prokaryotes. J. Mol. Biol. 2000, 301:75-100.
86. Saier M.H. Families of Transmembrane Sugar Transport Proteins. Mol. Microbiol. 2000, 35:699-710.
87. Saier M.H., Eng B.H., Fard S., Garg J., Haggerty D.A., Hutchinson W.J., Jack D.L., Lai E.C., Liu H.J., Nusinew D.P., Omar A.M., Pao S.S., Paulsen I.T., Quan J.A., Sliwinski M., Tseng T.-T., Wachi S., Young G.B. Phylogenetic Characterization of Novel Transport Families Revealed by Genome Analyses. Biochim. Biophys. Acta 1999, 1422:1-56.
88. Saier M.H. Families of Transmembrane Transporters Selective for Amino Acids and Their Derivatives. Microbiology 2000, 146:1775-1795.
89. Fann M.-C., Busch A., Maloney P.C. Functional Characterization of Cysteine Residues in GlpT, the Glycerol 3-Phosphate Transporter of Escherichia coli. J. Bacteriol. 2003, 185:3863-3870.
90. Huang Y., Lemieux M.J., Song J., Auer M., Wang D.-N. Structure and Mechanism of the Glycerol-3-Phosphate Transporter from Escherichia coli. Science 2003, 301(5633):616-620.
91. Abramson J., Kaback H.R., Iwata S. Structural Comparison of Lactose Permease and the Glycerol-3-Phosphate Antiporter: Members of the Major Facilitator Superfamily. Curr. Opin. Struct. Biol. 2004, 14:413-419.
92. Law C.J., Yang Q., Soudant C., Maloney P.C., Wang D.-N. Kinetic Evidence Is Consistent with the Rocker-Switch Mechanism of Membrane Transport by GlpT. Biochemistry 2007, 46:12190-12197.
93. Law C.J., Maloney P.C., Wang D.-N. Ins and Outs of Major Facilitator Superfamily Antiporters. Annu. Rev. Microbiol. 2008, 62(1):289-305.
94. Lemieux M.J., Song J., Kim M.J., Huang Y., Villa A., Auer M., Li X.-D., Wang D.-N. Three-Dimensional Crystallization of the Escherichia coli Glycerol-3-Phosphate Transporter: A Member of the Major Facilitator Superfamily. Protein Sci. 2003, 12(12):2748-2756.
95. Lemieux M., Huang Y., Wang D. The Structural Basis of Substrate Translocation by the Glycerol-3-Phosphate Transporter: A Member of the Major Facilitator Superfamily. Curr. Opin. Struct. Biol. 2004, 14(4):405-412.
96. Lemieux M.J., Huang Y., Wang D.-N. Glycerol-3-Phosphate Transporter of Escherichia coli: Structure, Function and Regulation. Res. Microbiol. 2004, 155(8):623-629.
97. Aksimentiev A., Schulten K. Imaging alpha-Hemolysin with Molecular Dynamics: Ionic Conductance, Osmotic Permeability and the Electrostatic Potential Map. Biophys. J. 2005, 88:3745-3761.
98. Wang Y., Tajkhorshid E. Electrostatic Funneling of Substrate in Mitochondrial Inner Membrane Carriers. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:9598-9603.
99. Maloney P.C., Ambudkar S.V., Anatharam V., Sonna L.A., Varadhachary A. Anion-Exchange Mechanisms in Bacteria. Microbiol. Mol. Biol. Rev. 1990, 54(1):1-17.
100. Law C.J., Almqvist J., Bernstein A., Goetz R.M., Huang Y., Soudant C., Laaksonen A., Hovmöller S., Wang D.-N. Salt-Bridge Dynamics Control Substrate-Induced Conformational Change in the Membrane Transporter GlpT. J. Mol. Biol. 2008, 378:828-839.
101. +/Sugar Symport. Science 2008, 321:810-814.
102. +-Symporters with Inverted Repeats. Curr. Opin. Struct. Biol. 2009, 19:425-432.
103. +/Glucose Cotransporter SGLT1. J. Biol. Chem. 1996, 271:1925-1934.
104. Hirayama B.A., Loo D.D.F., Díez-Sampedro A., Leung D.W., Meinild A.-K., Lai-Bing M., Turk E., Wright E.M. Sodium-Dependent Reorganization of the Sugar-Binding Site of SGLT1. Biochemistry 2007, 46:13391-13406.
105. Holland I.B., Cole S.P., Kuchler K., Higgins C.F. ABC Proteins: From Bacteria to Man 2003, Academic Press, London.
106. Oldham M.L., Davidson A.L., Chen J. Structural Insights into ABC Transporter Mechanism. Curr. Opin. Struct. Biol. 2008, 18(6):726-733.
107. Rees D.C., Johnson E., Lewinson O. ABC Transporters: The Power to Change. Nat. Rev. Mol. Cell Biol. 2009, 10(3):218-227.
108. Aller S.G., Yu J., Ward A., Weng Y., Chittaboina S., Zhuo R., Harrell P.M., Trinh Y.T., Zhang Q., Urbatsch I.L., Chang G. Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding. Science 2009, 323(5922):1718-1722.
109. Jin M.S., Oldham M.L., Zhang Q., Chen J. Crystal Structure of the Multidrug Transporter P-Glycoprotein from Caenorhabditis elegans. Nature 2012, 490(7421):566-569.
110. Ward A.B., Szewczyk P., Grimard V., Lee C.-W., Martinez L., Doshi R., Caya A., Villaluz M., Pardon E., Cregger C., Swartz D.J., Falson P.G., Urbatsch I.L., Govaerts C., Steyaert J., Chang G. Structures of P-Glycoprotein Reveal Its Conformational Flexibility and an Epitope on the Nucleotide-Binding Domain. Proc. Natl. Acad. Sci. U. S. A. 2013, 110(33):13386-13391.
111. Li J., Jaimes K.F., Aller S.G. Refined Structures of Mouse p-Glycoprotein. Proc. Natl. Acad. Sci. U. S. A. 2014, 23(1):34-36.
112. Dawson R.J., Locher K.P. Structure of the Multidrug ABC Transporter Sav 1866 from Staphylococcus aureus in Complex with AMP-PNP. FEBS Lett. 2007, 581(5):935-938.
113. Ward A., Reyes C.L., Yu J., Roth C.B., Chang G. Flexibility in the ABC Transporter MsbA: Alternating Access with a Twist. Proc. Natl. Acad. Sci. U. S. A. 2007, 104(48):19005-19010.
114. 12 Transporter BtuCD-F. Nature 2012, 490(7420):362-372.
115. Oswald C., Holland I.B., Schmitt L. The Motor Domains of ABC-Transporters. What Can Structures Tell Us?. Naunyn Schmiedebergs Arch. Pharmacol. 2006, 372(6):385-399.
116. Moussatova A., Kandt C., O'Mara M.L., Tieleman D.P. ATP-Binding Cassette Transporters in Escherichia coli. Biochim. Biophys. Acta 2008, 1778(9):1757-1771.
117. Chen J.Z., Fürst J., Chapman M.S., Grigorieff N. Low-Resolution Structure Refinement in Electron Microscopy. J. Struct. Biol. 2003, 144:144-151.
118. Becker J.-P., Bambeke F.V., Tulkens P.M., Prévost M. Dynamics and Structural Changes Induced by ATP Binding in SAV1866, a Bacterial ABC Exporter. J. Phys. Chem. B 2010, 114(48):15948-15957.
119. Zaitseva J., Jenewein S., Jumpertz T., Holland I.B., Schmitt L. H662 Is the Linchpin of ATP Hydrolysis in the Nucleotide-Binding Domain of the ABC Transporter HlyB. EMBO J. 2005, 24(11):1901-1910.
120. Wen P.-C., Verhalen B., Wilkens S., Mchaourab H.S., Tajkhorshid E. On the Origin of Large Flexibility of P-Glycoprotein in the Inward-Facing State. J. Biol. Chem. 2013, 288(26):19211-19220.
121. Yin Y., Jensen M.Ø., Tajkhorshid E., Schulten K. Sugar Binding and Protein Conformational Changes in Lactose Permease. Biophys. J. 2006, 91:3972-3985.
122. Jensen M.Ø., Yin Y., Tajkhorshid E., Schulten K. Sugar Transport Across Lactose Permease Probed by Steered Molecular Dynamics. Biophys. J. 2007, 93:92-102.
123. Thomas A.G., O'Driscoll C.M., Bressler J., Kaufmann W., Rojas C.J., Slusher B.S. Small Molecule Glutaminase Inhibitors Block Glutamate Release from Stimulated Microglia. Biochem. Biophys. Res. Commun. 2014, 443(1):32-36.
124. Jiang J., Amara S.G. New Views of Glutamate Transporter Structure and Function: Advances and Challenges. Neuropharmacology 2011, 60:172-181.
125. Zerangue N., Kavanaugh M.P. Flux Coupling in a Neuronal Glutamate Transporter. Nature 1996, 383:634-637.
126. Akyuz N., Altman R.B., Blanchard S.C., Boudker O. Transport Dynamics in a Glutamate Transporter Homologue. Nature 2013, 502:114-118.
127. +-Dependent Aspartate Transporter from Pyrococcus horikoshii. J. Biol. Chem. 2009, 284:17540-17548.
128. Grewer C., Balani P., Weidenfeller C., Bartusel T., Tao Z., Tauen T. Individual Subunits of the Glutamate Transporter EAAC1 Homotrimer Function Independently of Each Other. Biochemistry 2005, 44:11913-11923.
129. ph Is Regulated by the Movements of the Helical Hairpin HP2. J. Biol. Chem. 2013, 288(12):8231-8237.
130. Zhang Z., Tao Z., Gameiro A., Barcelona S., Braams S., Rauen T. Transport Direction Determines the Kinetics of Substrate Transport by the Glutamate Transporter EAAC1. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:18025-18030.
131. Newstead S., Drew D., Cameron A.D., Postis V.L., Xia X., Fowler P.W., Ingram J.C., Carpenter E.P., Sansom M.S., McPherson M.J., Baldwin S.A., Iwata S. Crystal Structure of a Prokaryotic Homologue of the Mammalian Oligopeptide-Proton Symporters, PepT1 and PepT2. EMBO J. 2011, 30(2):417-426.
132. Solcan N., Kwok J., Fowler P.W., Cameron A.D., Drew D., Iwata S., Newstead S. Alternating Access Mechanism in the POT Family of Oligopeptide Transporters: Alternating Access Mechanism in the POT Family. EMBO J. 2012, 31(16):3411-3421.
133. Johnson E.A., Tanford C., Reynolds J.A. Variable Stoichiometry in Active Ion Transport: Theoretical Analysis of Physiological Consequences. Proc. Natl. Acad. Sci. U. S. A. 1985, 82(16):5352-5356.
134. Borbat P.P., Surendhran K., Bortolus M., Zou P., Freed J.H., Mchaourab H.S. Conformational Motion of the ABC Transporter MsbA Induced by ATP Hydrolysis. PLoS Biol. 2007, 5(10):e271.
135. Zou P., Bortolus M., Mchaourab H.S. Conformational Cycle of the ABC Transporter MsbA in Liposomes: Detailed Analysis Using Double Electron-Electron Resonance Spectroscopy. J. Mol. Biol. 2009, 393(3):586-597.
136. Doshi R., Woebking B., van Veen H.W. Dissection of the Conformational Cycle of the Multidrug/LipidA ABC Exporter MsbA. Proteins 2010, 78(14):2867-2872.
137. Cooper R.S., Altenberg G.A. Association/Dissociation of the Nucleotide-Binding Domains of the ATP-Binding Cassette Protein MsbA Measured During Continuous Hydrolysis. J. Biol. Chem. 2013, 288(29):20785-20796.
138. Jones P.M., George A.M. Mechanism of ABC Transporters: A Molecular Dynamics Simulation of a Well Characterized Nucleotide-Binding Subunit. Proc. Natl. Acad. Sci. U. S. A. 2002, 99(20):12639-12644.
139. 12 ATP-Binding Cassette (ABC) Transporter BtuCD. J. Biol. Chem. 2004, 279(43):45013-45019.
140. Campbell J.D., Sansom M.S. Nucleotide Binding to the Homodimeric MJ0796 Protein: A Computational Study of a Prokaryotic ABC Transporter NBD Dimer. FEBS Lett. 2005, 579(19):4193-4199.
141. Oloo E.O., Fung E.Y., Tieleman D.P. The Dynamics of the MgATP-Driven Closure of MalK, the Energy-Transducing Subunit of the Maltose ABC Transporter. J. Biol. Chem. 2006, 281(38):28397-28407.
142. Ivetac A., Campbell J.D., Sansom M.S. Dynamics and Function in a Bacterial ABC Transporter: Simulation Studies of the BtuCDF System and Its Components. Biochemistry 2007, 46(10):2767-2778.
143. Sonne J., Kandt C., Peters G.H., Hansen F.Y., Jansen M.O., Tieleman D.P. Simulation of the Coupling Between Nucleotide Binding and Transmembrane Domains in the ATP Binding Cassette Transporter BtuCD. Biophys. J. 2007, 92(8):2727-2734.
144. Jones P.M., George A.M. Nucleotide-Dependent Allostery Within the ABC Transporter ATP-Binding Cassette. J. Biol. Chem. 2007, 282(31):22793-22803.
145. Wieczorek G., Zielenkiewicz P. δF508 Mutation Increases Conformational Flexibility of CFTR Protein. J. Cyst. Fibros. 2008, 7(4):295-300.
146. Jones M.K., Catte A., Patterson J.C., Gu F., Chen J., Li L., Segrest J.P. Thermal Stability of Apolipoprotein A-I in High-Density Lipoproteins by Molecular Dynamics. Biophys. J. 2009, 96:954-971.
147. 12 ABC Transporter BtuCD. Proteins 2010, 78(3):738-753.
148. Oliveira A.S., Baptista A.M., Soares C.M. Conformational Changes Induced by ATP-Hydrolysis in an ABC Transporter: A Molecular Dynamics Study of the SAV1866 Exporter. Proteins 2011, 79(6):1977-1990.
149. 2E Complex. PLoS Comput. Biol. 2011, 7(8):e1002128.
150. Jones P.M., George A.M. Molecular-Dynamics Simulations of the ATP/apo State of a Multidrug ATP-Binding Cassette Transporter Provide a Structural and Mechanistic Basis for the Asymmetric Occluded State. Biophys. J. 2011, 100(12):3025-3034.
151. St-Pierre J.-F., Bunker A., Róg T., Karttunen M., Mousseau N. Molecular Dynamics Simulations of the Bacterial ABC Transporter SAV1866 in the Closed Form. J. Phys. Chem. B 2012, 116(9):2934-2942.
152. Mehmood S., Domene C., Forest E., Jault J.-M. Dynamics of a Bacterial Multidrug ABC Transporter in the Inward- and Outward-Facing Conformations. Proc. Natl. Acad. Sci. U. S. A. 2012, 109(27):10832-10836.
153. Jones P.M., George A.M. Role of the D-Loops in Allosteric Control of ATP Hydrolysis in an ABC Transporter. J. Phys. Chem. A 2012, 116(11):3004-3013.
154. Liu M., Hou T., Feng Z., Li Y. The Flexibility of P-Glycoprotein for Its Poly-Specific Drug Binding from Molecular Dynamics Simulations. J. Biomol. Struct. Dyn. 2013, 31(6):612-629.
155. George A.M., Jones P.M. An Asymmetric Post-Hydrolysis State of the ABC Transporter ATPase Dimer. PLoS One 2013, 8(4):e59854.
156. Verhalen B., Ernst S., Börsch M., Wilkens S. Dynamic Ligand-Induced Conformational Rearrangements in P-Glycoprotein as Probed by Fluorescence Resonance Energy Transfer Spectroscopy. J. Biol. Chem. 2012, 287(2):1112-1127.
157. Al-Shawi M.K., Omote H. The Remarkable Transport Mechanism of P-Glycoprotein: A Multidrug Transporter. J. Bioenerg. Biomembr. 2005, 37(6):489-496.
158. Orelle C., Ayvaz T., Everly R.M., Klug C.S., Davidson A.L. Both Maltose-Binding Protein and ATP Are Required for Nucleotide-Binding Domain Closure in the Intact Maltose ABC Transporter. Proc. Natl. Acad. Sci. U. S. A. 2008, 105(35):12837-12842.
159. Izrailev S., Stepaniants S., Balsera M., Oono Y., Schulten K. Molecular Dynamics Study of Unbinding of the Avidin-Biotin Complex. Biophys. J. 1997, 72:1568-1581.
160. Moradi M., Babin V., Roland C., Sagui C. Reaction Path Ensemble of the B-Z-DNA Transition: A Comprehensive Atomistic Study. Nucleic Acids Res. 2013, 41(1):33-43.
161. Moradi M., Sagui C., Roland C. Calculating Relative Transition Rates with Driven Nonequilibrium Simulations. Chem. Phys. Lett. 2011, 518:109-113.
162. Moradi M., Sagui C., Roland C. Investigating Rare Events with Nonequilibrium Work Measurements: I. Nonequilibrium Transition Path Probabilities. J. Chem. Phys. 2014, 140(3):034114.
163. Moradi M., Sagui C., Roland C. Investigating Rare Events with Nonequilibrium Work Measurements: II. Transition and Reaction Rates. J. Chem. Phys. 2014, 140(3):034115.
164. Zeuthen T. Water-Transporting Proteins. J. Membr. Biol. 2010, 234(2):57-73.
165. i Cotransporters. Channels 2008, 2:346-357.
166. Conde A., Diallinas G., Chaumont F., Chaves M., Gerós H. Transporters, Channels, or Simple Diffusion? Dogmas, Atypical Roles and Complexity in Transport Systems. Int. J. Biochem. Cell Biol. 2010, 42:857-868.
167. Zeuthen T., Stein W.D. Cotransport of Salt and Water in Membrane Proteins: Membrane Proteins as Osmotic Engines. J. Membr. Biol. 1994, 137:179-195.
168. +/Glucose Cotransport. Proc. Natl. Acad. Sci. U. S. A. 2001, 98(7):3796-3801.
169. +/Glucose Cotransport. Biophys. J. 2004, 86:125-133.
170. Naftalin R.J. Osmotic Water Transport with Glucose in GLUT2 and SGLT. Biophys. J. 2008, 94:3912-3923.
171. Singh S.K., Yamashita A., Gouaux E. Antidepressant Binding Site in a Bacterial Homologue of Neurotransmitter Transporters. Nature 2007, 448(7156):952-956.
172. Penmatsa A., Wang K.H., Gouaux E. X-Ray Structure of Dopamine Transporter Elucidates Antidepressant Mechanism. Nature 2013, 503:85-90.
173. Li J., Shaikh S.A., Enkavi G., Wen P.-C., Huang Z., Tajkhorshid E. Transient Formation of Water-Conducting States in Membrane Transporters. Proc. Natl. Acad. Sci. U. S. A. 2013, 110(19):7696-7701.
174. +/Glucose Cotransporter. Proc. Natl. Acad. Sci. U. S. A. 1996, 93(23):13367-13370.
175. +-Glucose Cotransporter Is a Molecular Water Pump. J. Physiol. 1998, 508(Pt 1):15-21.
176. Loo D.D., Hirayama B.A., Meinild A.K., Chandy G., Zeuthen T., Wright E.M. Passive Water and Ion Transport by Cotransporters. J. Physiol. 1999, 518(1):195-202.
177. +-Coupled Sugar Transporters (SGLT1). J. Physiol. 2002, 542(Pt 1):71-87.
178. Choe S., Rosenberg J.M., Abramson J., Wright E.M., Grabe M. Water Permeation Through the Sodium-Dependent Galactose Cotransporter vSGLT. Biophys. J. 2010, 99(7):L56-L58.
179. Sasseville L.J., Cuervo J.E., Lapointe J.-Y., Noskov S.Y. The Structural Pathway for Water Permeation Through Sodium-Glucose Cotransporters. Biophys. J. 2011, 101(8):1887-1895.
180. +-Coupled Cotransporters of Glucose (SGLT1) and of Iodide (NIS). The Dependence of Substrate Size Studied at High Resolution. J. Physiol. 2006, 570(Pt 3):485-499.
181. 2O in Porcine Retinal Pigment Epithelial Cells. Exp. Eye Res. 2003, 76(4):493-504.
182. Santacroce M., Castagna M., Sacchi V.F. Passive Water Permeability of Some Wild Type and Mutagenized Amino Acid Cotransporters of the SLC6/NSS Family Expressed in Xenopus laevis Oocytes. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2010, 156(4):509-517.
183. +-Induced Leak Current in the Rat Gamma-Aminobutyric Acid (GABA) Transporter-1. J. Physiol. 2002, 544(Pt 2):447-458.
184. Fischbarg J., Kuang K.Y., Vera J.C., Arant S., Silverstein S.C., Loike J., Rosen O.M. Glucose Transporters Serve as Water Channels. Proc. Natl. Acad. Sci. U. S. A. 1990, 87(8):3244-3247.
185. Zeuthen T., Zeuthen E., Macaulay N. Water Transport by GLUT2 Expressed in Xenopus laevis Oocytes. J. Physiol. 2007, 579(2):345-361.
186. +/Glucose Cotransporter SGLT1. Biophys. J. 2010, 98:231-239.
187. Henderson P. Proton-Linked Sugar Transport Systems in Bacteria. J. Bioenerg. Biomembr. 1990, 22:525-569.
188. Bush D.R. Proton-Coupled Sugar and Amino-Acid Transporters in Plants. Annu. Rev. Plant Physiol. Plant Mol. Biol. 1993, 44:513-542.
189. Hediger M.A. Structure, Function and Evolution of Solute Transporters in Prokaryotes and Eukaryotes. J. Exp. Biol. 1994, 196:15-49.
190. Wipf D., Ludewig U., Tegeder M., Rentsch D., Koch W., Frommer W.B. Conservation of Amino Acid Transporters in Fungi, Plants and Animals. Trends Biochem. Sci. 2002, 27:139-147.
191. Pittman J.K., Edmond C., Sunderland P.A., Bray C.M. A Cation-Regulated and Proton Gradient-Dependent Cation Transporter from Chlamydomonas reinhardtii Has a Role in Calcium and Sodium Homeostasis. J. Biol. Chem. 2009, 284:525-533.
192. +-Coupled Nutrient, Micronutrient and Drug Transporters in the Mammalian Small Intestine. Exp. Physiol. 2007, 92:603-619.
193. Thwaites D.T., Anderson C.M. The slc36 Family of Proton-Coupled Amino Acid Transporters and Their Potential Role in Drug Transport. Br. J. Pharmacol. 2011, 164:1802-1816.
194. Marx D. Proton Transfer 200 Years After von Grotthuss: Insights from Ab Initio Simulations. ChemPhysChem 2006, 7(9):1848-1870.
195. Warshel A., Weiss R.M. An Empirical Valence Bond Approach for Comparing Reactions in Solution and in Enzymes. J. Am. Chem. Soc. 1980, 102:6218.
196. Day T.J.F., Soudackov A.V., Cuma M., Schmitt U.W., Voth G.A. A Second Generation Multistate Empirical Valence Bond Model for Proton Transport in Aqueous Systems. J. Chem. Phys. 2002, 117(12):5839.
197. Lammers S., Lutz S., Meuwly M. Reactive Force Fields for Proton Transfer Dynamics. J. Comput. Chem. 2008, 29(7):1048-1063.
198. - Transporters. Proc. Natl. Acad. Sci. U. S. A. 2014, 111:1819-1824.
199. + Exchanger. Proc. R. Soc. Lond. B Biol. Sci. 2009, 364:175-180.
200. Miller C. ClC Chloride Channels Viewed Through a Transporter Lens. Nature 2006, 440(7083):484-489.
201. Lisal J., Maduke M. Proton-Coupled Gating in Chloride Channels. Proc. R. Soc. Lond. B Biol. Sci. 2009, 364:181-187.
202. Mindell J.A. The Tao of Chloride Transporter Structure. Science 2010, 330:601-602.
203. Dutzler R., Campbell E.B., Cadene M., Chait B.T., MacKinnon R. X-Ray Structure of a ClC Chloride Channel at 3.0Å Reveals the Molecular Basis of Anion Selectivity. Nature 2002, 415:287-294.
204. Accardi A., Lobet S., Williams C., Miller C., Dutzler R. Synergism Between Halide Binding and Proton Transport in a CLC-Type Exchanger. J. Mol. Biol. 2006, 362:691-699.
205. + Exchange Transporter by Polyatomic Anions. J. Mol. Biol. 2006, 362:682-690.
206. + Exchanger. J. Gen. Physiol. 2005, 126:563-570.
207. + Exchanger. J. Gen. Physiol. 2009, 133:131-138.
208. Agmon N. The Grotthuss Mechanism. Chem. Phys. Lett. 1995, 244(5):456-462.