Shimon Schuldiner

Summary

Affiliation: The Hebrew University
Country: Israel

Publications

  1. ncbi request reprint In vitro monomer swapping in EmrE, a multidrug transporter from Escherichia coli, reveals that the oligomer is the functional unit
    D Rotem
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 276:48243-9. 2001
  2. ncbi request reprint Competition as a way of life for H(+)-coupled antiporters
    Shimon Schuldiner
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel Electronic address
    J Mol Biol 426:2539-46. 2014
  3. pmc Undecided membrane proteins insert in random topologies. Up, down and sideways: it does not really matter
    Shimon Schuldiner
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Trends Biochem Sci 37:215-9. 2012
  4. ncbi request reprint When biochemistry meets structural biology: the cautionary tale of EmrE
    Shimon Schuldiner
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Trends Biochem Sci 32:252-8. 2007
  5. ncbi request reprint Small is mighty: EmrE, a multidrug transporter as an experimental paradigm
    S Schuldiner
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    News Physiol Sci 16:130-4. 2001
  6. doi request reprint EmrE, a model for studying evolution and mechanism of ion-coupled transporters
    Shimon Schuldiner
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Biochim Biophys Acta 1794:748-62. 2009
  7. pmc Characterization of bacterial drug antiporters homologous to mammalian neurotransmitter transporters
    Eyal Vardy
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    J Bacteriol 187:7518-25. 2005
  8. ncbi request reprint Exploring the binding domain of EmrE, the smallest multidrug transporter
    Michal Sharoni
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 280:32849-55. 2005
  9. pmc Identification of a glycine motif required for packing in EmrE, a multidrug transporter from Escherichia coli
    Yael Elbaz
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 283:12276-83. 2008
  10. ncbi request reprint On parallel and antiparallel topology of a homodimeric multidrug transporter
    Misha Soskine
    Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 281:36205-12. 2006

Collaborators

  • A Rothman
  • P Dibrov
  • Yitzhak Pilpel
  • Gideon Schreiber
  • Eitan Bibi
  • Isaiah T Arkin
  • Christopher G Tate
  • Adam B Weinglass
  • Kay Eberhard Gottschalk
  • HOWARD KABACK
  • J P Whitelegge
  • Sonia Steiner-Mordoch
  • Yael Elbaz
  • Iris Nasie
  • H Yerushalmi
  • Misha Soskine
  • Yoav Adam
  • Dvir Rotem
  • Eyal Vardy
  • Dana Yaffe
  • Yael Gros
  • E Padan
  • Shira Ninio
  • Naama Tayer
  • Yelena Ugolev
  • Shlomo Brill
  • D Rotem
  • Ayala Gold
  • Nir Tal
  • E Pinner
  • Tsafi Danieli
  • Vipin Agarwal
  • M Lebendiker
  • Michal Sharoni
  • Nadejda Sigal
  • S S Mordoch
  • Natalia Gutman
  • Iban Ubarretxena-Belandia
  • Tali Segal
  • Lucy R Forrest
  • Yonatan Shuster
  • Sebastian Radestock
  • Ofir Sade Falk
  • S Ninio
  • Baruch I Kanner
  • Dalia Solomon
  • R Yelin
  • Robert H Edwards
  • Tal Salomon
  • Michal Yechieli
  • Uwe Fink
  • Bernd Reif
  • Shirley Mark
  • Roy Mizrachi
  • Asa Eitan
  • Emmanuelle Steinfels
  • D Taglicht
  • Shahar Molshanski-Mor
  • Y Olami
  • Joyce M Baldwin
  • A Rimon
  • O Carmel
  • N Sal-man
  • R Karpel
  • Y Gerchman
  • M Harel-Bronstein
  • D Granot
  • O Rahav-Manor
  • Y Stern-Bach
  • D Kirsch
  • N Dover
  • G Glaser
  • Y Kotler
  • J N Keen
  • S Steiner-Mordoch
  • G Rudnick
  • H Bercovier
  • M Wallach
  • M Bejerano
  • J B Findlay
  • S Sela
  • S S Steiner-Mordoch
  • I Flechner
  • N Greenberg-Ofrath
  • H Fishkes
  • T Alon
  • N Maisler

Detail Information

Publications73

  1. ncbi request reprint In vitro monomer swapping in EmrE, a multidrug transporter from Escherichia coli, reveals that the oligomer is the functional unit
    D Rotem
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 276:48243-9. 2001
    ..In addition, sulfhydryl reagents inhibit the above hetero-oligomer even though Cys residues are present only in the inactive monomer. It is concluded that, in EmrE, the oligomer is the functional unit...
  2. ncbi request reprint Competition as a way of life for H(+)-coupled antiporters
    Shimon Schuldiner
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel Electronic address
    J Mol Biol 426:2539-46. 2014
    ..In this review, I discuss in detail the case of EmrE, a multidrug transporter from Escherichia coli and evaluate the information available for other H(+)-coupled antiporters. ..
  3. pmc Undecided membrane proteins insert in random topologies. Up, down and sideways: it does not really matter
    Shimon Schuldiner
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Trends Biochem Sci 37:215-9. 2012
    ..This unique phenomenon provides strong support for a simple mechanism of transport where the directionality is determined solely by the driving force...
  4. ncbi request reprint When biochemistry meets structural biology: the cautionary tale of EmrE
    Shimon Schuldiner
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Trends Biochem Sci 32:252-8. 2007
    ..The 3D structures of EmrE have since been retracted because of faulty software, but the suggestion that the protomers in the dimer are in an antiparallel topological orientation sparked controversy that is still ongoing...
  5. ncbi request reprint Small is mighty: EmrE, a multidrug transporter as an experimental paradigm
    S Schuldiner
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    News Physiol Sci 16:130-4. 2001
    ..In each monomer there are four tightly packed transmembrane segments and one membrane-embedded charged residue. This residue provides the basis for the coupling mechanism as part of a binding site "time shared" by substrates and protons...
  6. doi request reprint EmrE, a model for studying evolution and mechanism of ion-coupled transporters
    Shimon Schuldiner
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Biochim Biophys Acta 1794:748-62. 2009
    ..Furthermore, based on the findings that the cell multidrug transporters interact functionally we introduce the concept of a cell Resistosome...
  7. pmc Characterization of bacterial drug antiporters homologous to mammalian neurotransmitter transporters
    Eyal Vardy
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    J Bacteriol 187:7518-25. 2005
    ..Measurement of antibiotic accumulation in cells revealed proton motive force-dependent transport of those compounds...
  8. ncbi request reprint Exploring the binding domain of EmrE, the smallest multidrug transporter
    Michal Sharoni
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 280:32849-55. 2005
    ..Taken together the findings imply the existence of a binding cavity accessible to alkylating reagents where at least three residues from TM1, Tyr40 from TM2, and Trp63 in TM3 are involved in substrate binding...
  9. pmc Identification of a glycine motif required for packing in EmrE, a multidrug transporter from Escherichia coli
    Yael Elbaz
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 283:12276-83. 2008
    ..Upon substitution of glycine in these positions, the protein ability to form dimers is impaired as evaluated by cross-linking and pull-down experiments...
  10. ncbi request reprint On parallel and antiparallel topology of a homodimeric multidrug transporter
    Misha Soskine
    Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 281:36205-12. 2006
    ..We suggest that the antiparallel orientation observed is a result of the arrangement of the monomers in the crystal. Functionality of EmrE with the suggested antiparallel orientation of the monomers remains to be characterized...
  11. ncbi request reprint EmrE, a multidrug transporter from Escherichia coli, transports monovalent and divalent substrates with the same stoichiometry
    Dvir Rotem
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 279:48787-93. 2004
    ....
  12. ncbi request reprint Substrate-induced tryptophan fluorescence changes in EmrE, the smallest ion-coupled multidrug transporter
    Yael Elbaz
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Biochemistry 44:7369-77. 2005
    ..These findings strongly suggest the existence of an interaction between Trp63 and substrate, and the nature of this interaction can now be studied in more detail with the tools developed in this work...
  13. pmc Parallel topology of genetically fused EmrE homodimers
    Sonia Steiner-Mordoch
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    EMBO J 27:17-26. 2008
    ..The results support a parallel topology of the protomers in the functional dimer. The implications regarding insertion and evolution of membrane proteins are discussed...
  14. pmc The fast release of sticky protons: kinetics of substrate binding and proton release in a multidrug transporter
    Yoav Adam
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Proc Natl Acad Sci U S A 104:17989-94. 2007
    ....
  15. ncbi request reprint Direct evidence for substrate-induced proton release in detergent-solubilized EmrE, a multidrug transporter
    Misha Soskine
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    J Biol Chem 279:9951-5. 2004
    ..5 and for an aspartate replacement at the same position as 6.7. The high pK of the carboxyl at position 14 is essential for coupling of fluxes of protons and substrates...
  16. ncbi request reprint Identification of tyrosine residues critical for the function of an ion-coupled multidrug transporter
    Dvir Rotem
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 281:18715-22. 2006
    ..The role of these residues is discussed in the context of the published structures of EmrE...
  17. pmc Identification of molecular hinge points mediating alternating access in the vesicular monoamine transporter VMAT2
    Dana Yaffe
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Proc Natl Acad Sci U S A 110:E1332-41. 2013
    ..Residues at the anchor points are strongly conserved in other MFS transporters in one way or another, suggesting that interactions at these locations will be critical in most, if not all, MFS transporters...
  18. pmc In vitro synthesis of fully functional EmrE, a multidrug transporter, and study of its oligomeric state
    Yael Elbaz
    Protein Expression Facility, Wolfson Foundation Center for Applied Structural Biology, Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Proc Natl Acad Sci U S A 101:1519-24. 2004
    ..An additional interaction between dimers has been detected by using crosslinking between unique Cys residues. This finding implies the existence of a dimer of dimers...
  19. pmc EmrE, a small Escherichia coli multidrug transporter, protects Saccharomyces cerevisiae from toxins by sequestration in the vacuole
    R Yelin
    Alexander Silberman Institute of Life Sciences, Hebrew University, Jerusalem 91904, Israel
    J Bacteriol 181:949-56. 1999
    ..This novel way of detoxification has been previously suggested to function in organisms in which a large vacuolar compartment exists. This report represents the first molecular description of such a mechanism...
  20. ncbi request reprint An amino acid cluster around the essential Glu-14 is part of the substrate- and proton-binding domain of EmrE, a multidrug transporter from Escherichia coli
    Natalia Gutman
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 278:16082-7. 2003
    ..Taken as a whole, the results strongly support the concept of a common binding site for substrate and protons and stress the importance of one face of TM1 in substrate recognition, binding, and H(+)-coupled transport...
  21. ncbi request reprint Identification of residues in the translocation pathway of EmrE, a multidrug antiporter from Escherichia coli
    M Lebendiker
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 271:21193-9. 1996
    ..The results demonstrate the existence of a domain accessible only to substrates and provide a unique tool for studying the substrate permeation pathway of an ion-coupled transporter...
  22. pmc Topologically random insertion of EmrE supports a pathway for evolution of inverted repeats in ion-coupled transporters
    Iris Nasie
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 285:15234-44. 2010
    ..The results suggest that the small multidrug transporters are at an evolutionary junction and provide a model for the evolution of structure of transport proteins...
  23. pmc A coordinated network of transporters with overlapping specificities provides a robust survival strategy
    Nir Tal
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Proc Natl Acad Sci U S A 106:9051-6. 2009
    ..This strategy also confers evolvability to the organism by reducing constraints on change and allowing the accumulation of nonlethal variation...
  24. ncbi request reprint The membrane topology of EmrE - a small multidrug transporter from Escherichia coli
    Shira Ninio
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    FEBS Lett 562:193-6. 2004
    ..Our results support a secondary structure where the carboxy-terminus faces the cytoplasm, while the first loop faces the periplasm...
  25. ncbi request reprint Precious things come in little packages
    S Schuldiner
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    J Mol Microbiol Biotechnol 3:155-62. 2001
    ..Because of some of its properties and its size, EmrE provides a unique system to understand mechanisms of substrate recognition and translocation...
  26. ncbi request reprint An essential glutamyl residue in EmrE, a multidrug antiporter from Escherichia coli
    H Yerushalmi
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 275:5264-9. 2000
    ..Our results support the notion that Glu-14 is an essential part of a binding domain shared by substrates and protons but mutually exclusive in time. This notion provides the molecular basis for the obligatory exchange catalyzed by EmrE...
  27. ncbi request reprint Scanning cysteine accessibility of EmrE, an H+-coupled multidrug transporter from Escherichia coli, reveals a hydrophobic pathway for solutes
    S S Mordoch
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 274:19480-6. 1999
    ..The results imply very tight packing of the protein without any continuous aqueous domain. Based on the findings described in this work, we conclude that in EmrE the substrates are translocated through a hydrophobic pathway...
  28. pmc Transforming a drug/H+ antiporter into a polyamine importer by a single mutation
    Shlomo Brill
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Proc Natl Acad Sci U S A 109:16894-9. 2012
    ..This mutant provides a unique paradigm to understand the function and evolution of distinct modes of transport...
  29. pmc Crosslinking of membrane-embedded cysteines reveals contact points in the EmrE oligomer
    Misha Soskine
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Proc Natl Acad Sci U S A 99:12043-8. 2002
    ..This method should be useful for other proteins with cysteine residues in a low-dielectric environment...
  30. ncbi request reprint A single carboxyl mutant of the multidrug transporter EmrE is fully functional
    H Yerushalmi
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 276:12744-8. 2001
    ..This suggests that dicyclohexylcarbodiimide binding is sterically prevented by the substrate, supporting the contention that Glu-14, the reactive residue, is part of the substrate-binding site...
  31. ncbi request reprint A common binding site for substrates and protons in EmrE, an ion-coupled multidrug transporter
    H Yerushalmi
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904, Jerusalem, Israel
    FEBS Lett 476:93-7. 2000
    ..We conclude that Glu-14 is an essential part of a binding site, common to substrates and protons. The occupancy of this site is mutually exclusive and provides the basis of the simplest coupling of two fluxes...
  32. pmc Identification of conformationally sensitive residues essential for inhibition of vesicular monoamine transport by the noncompetitive inhibitor tetrabenazine
    Yelena Ugolev
    From the Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 288:32160-71. 2013
    ..Our results provide a novel insight into the mechanism of transport and TBZ binding by VMAT2. ..
  33. doi request reprint Topology determination of untagged membrane proteins
    Iris Nasie
    Department of Biological Chemistry, Hebrew University of Jerusalem, Jerusalem, Israel
    Methods Mol Biol 1033:121-30. 2013
    ..This technique, optimized for bacterial cells, allows the visualization of the protein in the native environment and incorporates the substituted-cysteine accessibility method. ..
  34. pmc New substrates on the block: clinically relevant resistances for EmrE and homologues
    Iris Nasie
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    J Bacteriol 194:6766-70. 2012
    ..Furthermore, our study of one of the homologues, a putative heterodimer, supports the suggestion that in the SMR family, heterodimers can also function as homodimers...
  35. ncbi request reprint Probing the conformation of NhaA, a Na+/H+ antiporter from Escherichia coli, with trypsin
    A Rothman
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    Biochemistry 36:14572-6. 1997
    ..Thus, upon activation, NhaA appears to undergo a change in conformation that is reflected in specific regions of the protein...
  36. ncbi request reprint NhaR, a protein homologous to a family of bacterial regulatory proteins (LysR), regulates nhaA, the sodium proton antiporter gene in Escherichia coli
    O Rahav-Manor
    Division of Microbial and Molecular Ecology, Hadassah Medical School, Hebrew University of Jerusalem, Israel
    J Biol Chem 267:10433-8. 1992
    ..Multicopy plasmid bearing nhaR does not change the phenotype of either OR200 or NM81. On the other hand, multicopy nhaA renders the cells Li(+)- and and Na(+)-resistant even without nhaR...
  37. ncbi request reprint Characterization of an archaeal multidrug transporter with a unique amino acid composition
    Shira Ninio
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 278:12000-5. 2003
    ..This phenomenon reveals significant sequence elements in small multidrug transporters...
  38. ncbi request reprint 3D model of the Escherichia coli multidrug transporter MdfA reveals an essential membrane-embedded positive charge
    Nadejda Sigal
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Biochemistry 44:14870-80. 2005
    ..Importantly, Arg112 is evolutionarily conserved in secondary drug transporters, and here we show that a positive charge at this position is absolutely essential for multidrug transport by MdfA...
  39. ncbi request reprint Amiloride and harmaline are potent inhibitors of NhaB, a Na+/H+ antiporter from Escherichia coli
    E Pinner
    Division of Microbial and Molecular Ecology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    FEBS Lett 365:18-22. 1995
    ..Clonidine is a poor inhibitor (K0.5 = 200 microM) while cimetidine had no effect on the antiporter up to concentration of 1 mM. These new potent inhibitors provide us with important tools for the study of the mechanism of action of NhaB...
  40. ncbi request reprint EmrE, an Escherichia coli 12-kDa multidrug transporter, exchanges toxic cations and H+ and is soluble in organic solvents
    H Yerushalmi
    Division of Microbial and Molecular Ecology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Givat Ram, Israel
    J Biol Chem 270:6856-63. 1995
    ..EmrE is a multidrug transporter of a novel type, and, because of its size and its solubility properties, it provides a unique model to study structure-function aspects of transport reactions in ion-coupled processes...
  41. ncbi request reprint A model for coupling of H(+) and substrate fluxes based on "time-sharing" of a common binding site
    H Yerushalmi
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    Biochemistry 39:14711-9. 2000
    ..The occupancy of this site by H(+) and substrate is mutually exclusive and provides the basis of the simplest coupling for two fluxes...
  42. pmc A single amino acid substitution (Glu134-->Ala) in NhaR1 increases the inducibility by Na+ of the product of nhaA, a Na+/H+ antiporter gene in Escherichia coli
    O Carmel
    Division of Microbial and Molecular Ecology, Hebrew University of Jerusalem, Israel
    EMBO J 13:1981-9. 1994
    ..Yet in this assay the DNA binding pattern of neither NhaR nor NhaR1 was affected by the addition of Na+. The possible relevance of these two DNA-binding complexes to the Na(+)-induced NhaR-mediated expression is discussed...
  43. pmc Histidine-226 is part of the pH sensor of NhaA, a Na+/H+ antiporter in Escherichia coli
    Y Gerchman
    Division of Microbial and Molecular Ecology, Hebrew University of Jerusalem, Israel
    Proc Natl Acad Sci U S A 90:1212-6. 1993
    ..5, H226R is reversibly inactivated above pH 7.5, reaching 10-20% of the maximal activity at pH 8.5. We suggest that His-226 is part of a pH-sensitive site that regulates the activity of NhaA...
  44. ncbi request reprint Functional analysis of novel multidrug transporters from human pathogens
    S Ninio
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 276:48250-6. 2001
    ..A comparative study of various homologous proteins provides a tool for deciphering structure-function relationship and monomer-monomer interaction in multidrug transporters and in membrane proteins in general...
  45. pmc Directed evolution reveals hidden properties of VMAT, a neurotransmitter transporter
    Yael Gros
    Department of Biological Chemistry, Alexander A Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 285:5076-84. 2010
    ..A process that has taken millions of years of evolution can be reversed by three mutations...
  46. pmc Expression of neurotransmitter transporters for structural and biochemical studies
    Yael Elbaz
    Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    Protein Expr Purif 73:152-60. 2010
    ..All were functional and expressed to high levels. Our results demonstrate the advantages of the baculovirus expression system for the expression of mammalian neurotransmitter transporters in a functional state...
  47. pmc Structural conservation in the major facilitator superfamily as revealed by comparative modeling
    Eyal Vardy
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, 91904 Israel
    Protein Sci 13:1832-40. 2004
    ..The models are based on the two MFS structures and on experimental data. The models for both proteins are in good agreement with the data available and support the notion of a shared fold for all MFS proteins...
  48. ncbi request reprint Negative dominance studies demonstrate the oligomeric structure of EmrE, a multidrug antiporter from Escherichia coli
    H Yerushalmi
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 271:31044-8. 1996
    ..The results described provide the first in vitro demonstration of the functional oligomeric structure of an ion-coupled transporter...
  49. ncbi request reprint Overproduction and purification of a functional Na+/H+ antiporter coded by nhaA (ant) from Escherichia coli
    D Taglicht
    Institute of Life Sciences, Hebrew University, Jerusalem, Israel
    J Biol Chem 266:11289-94. 1991
    ..The activation at alkaline pH values (2000-fold increase) is consistent with the proposed role of the antiporter in regulation of internal pH at the alkaline pH range...
  50. ncbi request reprint Proton-sodium stoichiometry of NhaA, an electrogenic antiporter from Escherichia coli
    D Taglicht
    Division of Microbial and Molecular Ecology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    J Biol Chem 268:5382-7. 1993
    ..2 and 8.1. These results support the suggestion that a change in the catalytic rate of NhaA rather than its stoichiometry is crucial for its role in regulation of intracellular pH in alkaline environments...
  51. ncbi request reprint Na+/H+ antiporters, molecular devices that couple the Na+ and H+ circulation in cells
    E Padan
    Division of Microbial and Molecular Ecology, Hebrew University of Jerusalem, Israel
    J Bioenerg Biomembr 25:647-69. 1993
    ..The identification of Histidine 226 in the "pH sensor" of NhaA is a step forward towards the understanding of the pH regulation of these proteins...
  52. ncbi request reprint Replacements of histidine 226 of NhaA-Na+/H+ antiporter of Escherichia coli. Cysteine (H226C) or serine (H226S) retain both normal activity and pH sensitivity, aspartate (H226D) shifts the pH profile toward basic pH, and alanine (H226A) inactivates the ca
    A Rimon
    Division of Microbial and Molecular Ecology, Hebrew University of Jerusalem, Israel
    J Biol Chem 270:26813-7. 1995
    ..It is suggested that charge modifies the pH profile but is not essential for the pH regulation of NhaA...
  53. ncbi request reprint Topological analysis of NhaA, a Na+/H+ antiporter from Escherichia coli
    A Rothman
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel
    J Biol Chem 271:32288-92. 1996
    ..The results support a 12-transmembrane segment model with the N and C termini located in the cytoplasm. The evidence indicates that two very short segments, 14 and 16 amino acids long, must cross the membrane in an unknown conformation...
  54. ncbi request reprint Sequencing of the gene ant which affects the Na+/H+ antiporter activity in Escherichia coli
    R Karpel
    Department of Molecular and Microbial Ecology, Hadassah Medical School, Hebrew University, Jerusalem, Israel
    J Biol Chem 263:10408-14. 1988
    ..The DNA fragment has been sequenced and found to contain an open reading frame of 1085 base pairs. Analysis of the sequence of the predicted protein suggests the presence of 10 putative transmembrane segments in the protein...
  55. ncbi request reprint EmrE, the smallest ion-coupled transporter, provides a unique paradigm for structure-function studies
    S Schuldiner
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    J Exp Biol 200:335-41. 1997
    ..In co-reconstitution experiments of wild-type protein with three different inactive mutants, negative dominance has been observed. This phenomenon suggests that EmrE is functional as a homo-oligomer...
  56. ncbi request reprint MH1, a second-site revertant of an Escherichia coli mutant lacking Na+/H+ antiporters (delta nhaA delta nhaB), regains Na+ resistance and a capacity to excrete Na+ in a delta microH(+)-independent fashion
    M Harel-Bronstein
    Division of Microbial and Molecular Ecology, Hebrew University of Jerusalem, Israel
    J Biol Chem 270:3816-22. 1995
    ..It is concluded that under some conditions (high K+ in the medium or in MH1-like mutants), a primary pump driven by respiration is responsible for Na+ extrusion when the Na+/H+ antiporters are not active...
  57. ncbi request reprint Physiological role of nhaB, a specific Na+/H+ antiporter in Escherichia coli
    E Pinner
    Division of Microbial and Molecular Ecology, Hebrew University of Jerusalem, Israel
    J Biol Chem 268:1729-34. 1993
    ....
  58. ncbi request reprint Deletion of ant in Escherichia coli reveals its function in adaptation to high salinity and an alternative Na+/H+ antiporter system(s)
    E Padan
    Department of Microbial and Molecular Ecology, Life Science Institute, Jerusalem, Israel
    J Biol Chem 264:20297-302. 1989
    ..Our results demonstrate the presence of an alternative Na+/H+ antiporter(s) in E. coli, additional to ant system...
  59. ncbi request reprint Molecular physiology of the Na+/H+ antiporter in Escherichia coli
    E Padan
    Department of Molecular and Microbial Ecology, Hebrew University of Jerusalem, Israel
    J Exp Biol 196:443-56. 1994
    ..5. Mutating all the histidines of NhaA shows that His-226 is part of the 'pH sensor' of NhaA...
  60. ncbi request reprint Cloning, sequencing and expression of the nhaA and nhaR genes from Salmonella enteritidis
    E Pinner
    Department of Molecular and Microbial Ecology, Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    Arch Microbiol 157:323-8. 1992
    ..The antiporter activity displays properties very similar to that of the E. coli NhaA, namely, it is activated by alkaline pH and recognizes Li+ with high affinity...
  61. ncbi request reprint Expression of a sodium proton antiporter (NhaA) in Escherichia coli is induced by Na+ and Li+ ions
    R Karpel
    Division of Microbial and Molecular Ecology, Hadassah Medical School, Hebrew University of Jerusalem, Israel
    J Biol Chem 266:21753-9. 1991
    ..At pH 7.5 maximal induction is obtained by 100 mM NaCl, whereas at pH 8.6, 10 mM NaCl elicit similar response. The pattern of regulation of nhaA reflects its importance in adaptation to high salinity and alkaline pH in E. coli...
  62. ncbi request reprint Cloning, sequencing, and expression of the nhaB gene, encoding a Na+/H+ antiporter in Escherichia coli
    E Pinner
    Department of Molecular and Microbiol Ecology, Hebrew University of Jerusalem, Israel
    J Biol Chem 267:11064-8. 1992
    ..In contrast to NhaA, whose activity increases with pH, NhaB is practically insensitive to pH. Limited homologies with Na+ transporters have been identified...
  63. ncbi request reprint Kinetic properties of NhaB, a Na+/H+ antiporter from Escherichia coli
    E Pinner
    Division of Microbial and Molecular Ecology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    J Biol Chem 269:26274-9. 1994
    ..The significance of the existence of two antiporters with different stoichiometries, NhaA and NhaB, active in the same cell, is discussed...
  64. doi request reprint Expression and function of the rat vesicular monoamine transporter 2
    Yoav Adam
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
    Am J Physiol Cell Physiol 294:C1004-11. 2008
    ..The reconstituted purified rVMAT2 has wild-type affinity for serotonin, and its turnover rate is approximately 0.4 substrate molecule/s...
  65. ncbi request reprint Identification and purification of a functional amine transporter from bovine chromaffin granules
    Y Stern-Bach
    Department of Molecular Biology, Hebrew University Hadassah Medical School, Ein Karem, Jerusalem, Israel
    J Biol Chem 265:3961-6. 1990
    ..In addition, binding of [3H]reserpine is accelerated upon imposition of a pH gradient across the proteoliposome. From these findings it is evident that a single polypeptide catalyzes the various functions of the transporter...
  66. pmc Homology of a vesicular amine transporter to a gene conferring resistance to 1-methyl-4-phenylpyridinium
    Y Stern-Bach
    Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel
    Proc Natl Acad Sci U S A 89:9730-3. 1992
    ....
  67. ncbi request reprint Energetics of reserpine binding and occlusion by the chromaffin granule biogenic amine transporter
    G Rudnick
    Department of Molecular Biology, Hadassah Medical School, Hebrew University of Jerusalem, Israel
    Biochemistry 29:603-8. 1990
    ....
  68. pmc Three-dimensional structure of the bacterial multidrug transporter EmrE shows it is an asymmetric homodimer
    Iban Ubarretxena-Belandia
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    EMBO J 22:6175-81. 2003
    ..The most remarkable feature of the structure of EmrE is that it is an asymmetric homodimer. The possible arrangement of the two polypeptides in the EmrE dimer is discussed based on the 3D density map...
  69. ncbi request reprint MAS solid-state NMR studies on the multidrug transporter EmrE
    Vipin Agarwal
    Leibniz Institut fur Molekulare Pharmakologie FMP, Robert Rossle Str 10, D 13125 Berlin, Germany
    Biochim Biophys Acta 1768:3036-43. 2007
    ..These experiments allow to assign the chemical shift of the carboxylic carbon of E14. In addition, spectra are analyzed which are obtained in the presence and absence of the ligand TPP+...
  70. ncbi request reprint Controversy over EmrE structure
    Shimon Schuldiner
    Science 317:748-51; author reply 748-51. 2007
  71. ncbi request reprint Structural biology: the ins and outs of drug transport
    Shimon Schuldiner
    Nature 443:156-7. 2006
  72. pmc A structural model of EmrE, a multi-drug transporter from Escherichia coli
    Kay Eberhard Gottschalk
    Institut fur Chemie und Biochemie II, Technische Universitat Munchen, Garching, Germany
    Biophys J 86:3335-48. 2004
    ..The two crucial residues that couple proton fluxes with substrate binding in the homo-dimer of EmrE, Glu-14, have a spatial arrangement that agrees with proposed molecular mechanisms of transport...
  73. ncbi request reprint Exploring the role of a unique carboxyl residue in EmrE by mass spectrometry
    Adam B Weinglass
    Howard Hughes Medical Institute, Department of Physiology, Molecular Biology Institute, University of California Los Angeles, 90095 1662, USA
    J Biol Chem 280:7487-92. 2005
    ..Taken together with other biochemical data, the findings support a "time sharing" mechanism in which both Glu-14 residues in a dimer are involved in tetraphenylphosphonium and H(+) binding...