H R Kaback

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint The kamikaze approach to membrane transport
    H R Kaback
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles, California 90095 1662, USA
    Nat Rev Mol Cell Biol 2:610-20. 2001
  2. ncbi request reprint Helix packing in polytopic membrane proteins: the lactose permease of Escherichia coli
    H R Kaback
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90024 1662, USA
    Curr Opin Struct Biol 7:537-42. 1997
  3. pmc Ligand-induced conformational changes in the lactose permease of Escherichia coli: evidence for two binding sites
    J Wu
    Department of Physiology, Howard Hughes Medical Institute, University of California at Los Angeles 90024 1662, USA
    Protein Sci 3:2294-301. 1994
  4. ncbi request reprint Cys-scanning mutagenesis: a novel approach to structure function relationships in polytopic membrane proteins
    S Frillingos
    Howard Hughes Medical Institute, Departments of Physiology and Microbiology and Molecular Genetics, Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90024
    FASEB J 12:1281-99. 1998
  5. pmc The role of transmembrane domain III in the lactose permease of Escherichia coli
    M Sahin-Toth
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90024 1662, USA
    Protein Sci 3:2302-10. 1994
  6. ncbi request reprint Characterization of Glu126 and Arg144, two residues that are indispensable for substrate binding in the lactose permease of Escherichia coli
    M Sahin-Toth
    Howard Hughes Medical Institute, Department of Physiology, Molecular Biology Institute, University of California, Los Angeles 90095 1662, USA
    Biochemistry 38:813-9. 1999
  7. ncbi request reprint Dynamics of lactose permease of Escherichia coli determined by site-directed chemical labeling and fluorescence spectroscopy
    J Wu
    Howard Hughes Medical Institute, Department of Physiology and Microbiology, University of California, Los Angeles 90095 1662, USA
    Biochemistry 34:8257-63. 1995
  8. ncbi request reprint Thiol cross-linking of transmembrane domains IV and V in the lactose permease of Escherichia coli
    C D Wolin
    Howard Hughes Medical Institute, Departments of Physiology and of Microbiology and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90025 1662, USA
    Biochemistry 39:6130-5. 2000
  9. ncbi request reprint Probing the conformation of the lactose permease of Escherichia coli by in situ site-directed sulfhydryl modification
    S Frillingos
    Howard Hughes Medical Institute, University of California, Los Angeles, 90024 1570, USA
    Biochemistry 35:3950-6. 1996
  10. ncbi request reprint Ligand-induced changes in periplasmic loops in the lactose permease of Escherichia coli
    J Sun
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90095 1662, USA
    Biochemistry 37:8020-6. 1998

Collaborators

Detail Information

Publications45

  1. ncbi request reprint The kamikaze approach to membrane transport
    H R Kaback
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles, California 90095 1662, USA
    Nat Rev Mol Cell Biol 2:610-20. 2001
    ..Novel approaches that have been developed and applied to one membrane transport protein, the lactose permease from Escherichia coli, are now being used to study various other membrane proteins...
  2. ncbi request reprint Helix packing in polytopic membrane proteins: the lactose permease of Escherichia coli
    H R Kaback
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90024 1662, USA
    Curr Opin Struct Biol 7:537-42. 1997
    ..Using the lac permease as a paradigm, several site-directed biophysical and biochemical techniques are described which should be generally applicable...
  3. pmc Ligand-induced conformational changes in the lactose permease of Escherichia coli: evidence for two binding sites
    J Wu
    Department of Physiology, Howard Hughes Medical Institute, University of California at Los Angeles 90024 1662, USA
    Protein Sci 3:2294-301. 1994
    ..2 mM) does not alter quenching by either compound, whereas a higher concentration of ligand (10 mM) decreases the quenching constant for iodide by about 50% and for acrylamide by about 20%.(ABSTRACT TRUNCATED AT 250 WORDS)..
  4. ncbi request reprint Cys-scanning mutagenesis: a novel approach to structure function relationships in polytopic membrane proteins
    S Frillingos
    Howard Hughes Medical Institute, Departments of Physiology and Microbiology and Molecular Genetics, Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90024
    FASEB J 12:1281-99. 1998
    ..structure-function relationships in polytopic membrane proteins...
  5. pmc The role of transmembrane domain III in the lactose permease of Escherichia coli
    M Sahin-Toth
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90024 1662, USA
    Protein Sci 3:2302-10. 1994
    ..The observations demonstrate that although no residue per se appears to be essential, structural properties of helix III are important for active lactose transport...
  6. ncbi request reprint Characterization of Glu126 and Arg144, two residues that are indispensable for substrate binding in the lactose permease of Escherichia coli
    M Sahin-Toth
    Howard Hughes Medical Institute, Department of Physiology, Molecular Biology Institute, University of California, Los Angeles 90095 1662, USA
    Biochemistry 38:813-9. 1999
    ..The results extend the conclusion that a carboxylate at position 126 and a guanidinium group at position 144 are irreplaceable for substrate binding and support the idea that Arg144 plays a major role in substrate specificity...
  7. ncbi request reprint Dynamics of lactose permease of Escherichia coli determined by site-directed chemical labeling and fluorescence spectroscopy
    J Wu
    Howard Hughes Medical Institute, Department of Physiology and Microbiology, University of California, Los Angeles 90095 1662, USA
    Biochemistry 34:8257-63. 1995
    ..In striking contrast, mutants Pro28-->Cys and Pro31-->Cys react extremely slowly with MIANS in the absent of ligand, and TDG dramatically enhances reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)..
  8. ncbi request reprint Thiol cross-linking of transmembrane domains IV and V in the lactose permease of Escherichia coli
    C D Wolin
    Howard Hughes Medical Institute, Departments of Physiology and of Microbiology and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90025 1662, USA
    Biochemistry 39:6130-5. 2000
    ..The data provide strong support for the argument that Glu126 and Arg144 are within close proximity and suggest that an unpaired carboxylate at position 126 causes a structural change at the interface between helices IV and V...
  9. ncbi request reprint Probing the conformation of the lactose permease of Escherichia coli by in situ site-directed sulfhydryl modification
    S Frillingos
    Howard Hughes Medical Institute, University of California, Los Angeles, 90024 1570, USA
    Biochemistry 35:3950-6. 1996
    ..In addition, the results are consistent with the idea that lactose permease has two binding sites: one with higher affinity on the periplasmic surface of the membrane and another with lower affinity on the cytoplasmic surface...
  10. ncbi request reprint Ligand-induced changes in periplasmic loops in the lactose permease of Escherichia coli
    J Sun
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90095 1662, USA
    Biochemistry 37:8020-6. 1998
    ....
  11. ncbi request reprint Proteomics on full-length membrane proteins using mass spectrometry
    J le Coutre
    Howard Hughes Medical Institute, Departments of Physiology and of Microbiology and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles 90095, USA
    Biochemistry 39:4237-42. 2000
    ..Finally, using in-line LC-MS, unknown proteins can be identified from solubilized Escherichia coli membranes without prior purification...
  12. pmc Properties of permease dimer, a fusion protein containing two lactose permease molecules from Escherichia coli
    M Sahin-Toth
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90024 1662
    Proc Natl Acad Sci U S A 91:5421-5. 1994
    ..The approach is consistent with the contention that the functional unit of lactose permease is a monomer...
  13. ncbi request reprint In vitro folding of a membrane protein: effect of denaturation and renaturation on substrate binding by the lactose permease of Escherichia coli
    M M He
    Howard Hughes Medical Institute, Department of Microbiology, University of California, Los Angeles 90095 1662, USA
    Mol Membr Biol 15:15-20. 1998
    ..The results demonstrate that both low- and high-affinity binding, as well as ligand-induced conformational changes in the permease, can be denatured reversibly in vitro...
  14. ncbi request reprint Ligand-induced movement of helix X in the lactose permease from Escherichia coli: a fluorescence quenching study
    Q Wang
    Howard Hughes Medical Institute, Department of Physiology, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90024 1570, USA
    Biochemistry 36:14120-7. 1997
    ..R. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 5539-5543] in which substrate binding causes a conformational change resulting in movement of Glu325 to a nonpolar environment with a dramatic increase in pKa...
  15. ncbi request reprint Helix packing in the lactose permease of Escherichia coli: distances between site-directed nitroxides and a lanthanide
    J Voss
    Chemistry Department, University of California, Davis, California 95616 0935, USA
    Biochemistry 40:3184-8. 2001
    ....
  16. pmc A molecular mechanism for energy coupling in a membrane transport protein, the lactose permease of Escherichia coli
    H R Kaback
    Howard Hughes Medical Institute, Department of Physiology, Molecular Biology Institute, University of California, Los Angeles, CA 90095 1662, USA
    Proc Natl Acad Sci U S A 94:5539-43. 1997
    ....
  17. ncbi request reprint The last two cytoplasmic loops in the lactose permease of Escherichia coli comprise a discontinuous epitope for a monoclonal antibody
    J Sun
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90095 1662, USA
    Biochemistry 36:274-80. 1997
    ....
  18. ncbi request reprint Interaction between residues Glu269 (helix VIII) and His322 (helix X) of the lactose permease of Escherichia coli is essential for substrate binding
    M M He
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90095, USA
    Biochemistry 36:13688-92. 1997
    ..The observations are consistent with the notion that the interaction between Glu269 and His322 stabilizes the interface between helices V and VIII and thereby leads to binding of substrate...
  19. ncbi request reprint Cysteine-scanning mutagenesis of transmembrane domain XII and the flanking periplasmic loop in the lactose permease of EScherichia coli
    M M He
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90095 1662, USA
    Biochemistry 35:12909-14. 1996
    ..Hubbell, W. L., & Kaback, H. R. (1996) Biochemistry 35, 12915-12918], site-directed spin labeling of single-Cys mutants at positions 387-402 is used to demonstrate that transmembrane domain XII is in an alpha-helical conformation...
  20. ncbi request reprint Cysteine-scanning mutagenesis of helix II and flanking hydrophilic domains in the lactose permease of Escherichia coli
    S Frillingos
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90024 1570, USA
    Biochemistry 36:269-73. 1997
    ..The results demonstrate that although no residue per se in this region of the permease is irreplaceable, the surface of one face of helix II is important for active lactose transport...
  21. ncbi request reprint Thiol cross-linking of cytoplasmic loops in the lactose permease of Escherichia coli
    I Kwaw
    Howard Hughes Medical Institute, Departments of Physiology and of Microbiology and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles, California 90095 1662, USA
    Biochemistry 39:3134-40. 2000
    ..In addition, evidence is presented suggesting that ligand binding induces conformational alterations between loop IV/V and loop VIII/IX or X/XI...
  22. pmc Arg-302 facilitates deprotonation of Glu-325 in the transport mechanism of the lactose permease from Escherichiacoli
    M Sahin-Toth
    Howard Hughes Medical Institute, Department of Physiology, Molecular Biology Institute, University of California, Los Angeles, CA 90095-1662, USA
    Proc Natl Acad Sci U S A 98:6068-73. 2001
    ..These observations lend strong support for the argument that Arg-302 interacts with Glu-325 to facilitate deprotonation of the carboxylic acid during turnover...
  23. ncbi request reprint Effect of the lipid phase transition on the lactose permease from Escherichia coli
    W Zhang
    Howard Hughes Medical Institute, Departments of Physiology and Microbiology and Molecular Genetics, Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095 1662, USA
    Biochemistry 39:14538-42. 2000
    ....
  24. ncbi request reprint Tilting of helix I and ligand-induced changes in the lactose permease determined by site-directed chemical cross-linking in situ
    J Wu
    Howard Hughes Medical Institute, Molecular Biology Institute, University of California, Los Angeles 90095 1662, USA
    Biochemistry 37:15785-90. 1998
    ..Taken together, the results indicate that ligand binding induces a translational or scissors-like rigid body movement of helix I and/or VII at the periplasmic interface between the helices...
  25. pmc Helix packing of lactose permease in Escherichia coli studied by site-directed chemical cleavage
    J Wu
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90095 1662, USA
    Proc Natl Acad Sci U S A 92:9186-90. 1995
    ..The results suggest that helix V is in close proximity to helices VII and VIII with position 148 in the interface between the helices, position 149 facing helix VII, and position 147 facing the lipid bilayer...
  26. ncbi request reprint Site-directed sulfhydryl labeling of the lactose permease of Escherichia coli: helices IV and V that contain the major determinants for substrate binding
    I Kwaw
    Howard Hughes Medical Institute, Department of Physiology and Microbiology, Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095-1662, USA
    Biochemistry 40:10491-9. 2001
    ..Furthermore, positions that exhibit ligand-induced changes are located for the most part in the vicinity of the residues directly involved in substrate binding, as well as the cytoplasmic loop between helices IV and V...
  27. ncbi request reprint Estimating loop-helix interfaces in a polytopic membrane protein by deletion analysis
    C D Wolin
    Howard Hughes Medical Institute, Department of Physiology, Los Angeles, California 90025 1662, USA
    Biochemistry 38:8590-7. 1999
    ..More specifically, evidence is presented supporting the contention that Glu126 and Arg144 which are charge paired and critical for substrate binding are within helices IV and V, respectively...
  28. ncbi request reprint Membrane topology of helices VII and XI in the lactose permease of Escherichia coli studied by lacY-phoA fusion analysis and site-directed spectroscopy
    M L Ujwal
    Howard Hughes Medical Institute, Department of Physiology, Los Angeles, California, USA
    Biochemistry 34:14909-17. 1995
    ....
  29. ncbi request reprint Chemical rescue of Asp237-->Ala and Lys358-->Ala mutants in the lactose permease of Escherichia coli
    S Frillingos
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90024 1570, USA
    Biochemistry 35:13363-7. 1996
    ....
  30. ncbi request reprint Proximity of periplasmic loops in the lactose permease of Escherichia coli determined by site-directed cross-linking
    J Sun
    Howard Hughes Medical Institute, Department of Physiology, Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California 90095 1662, USA
    Biochemistry 36:11959-65. 1997
    ..U.S.A. 93, 14498-502] demonstrating that helices I and II are close to helices VII and XI. Finally, evidence is presented indicating that conformational flexibility between loops I/II and XI/XII may be important for permease turnover...
  31. ncbi request reprint Functional estimation of loop-helix boundaries in the lactose permease of Escherichia coli by single amino acid deletion analysis
    C D Wolin
    Howard Hughes Medical Institute, Department of Physiology, Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California 90025-1662, USA
    Biochemistry 40:1996-2003. 2001
    ..Thus, transmembrane domain VI which is probably on the periphery of the 12-helix bundle may make few functionally important contacts...
  32. ncbi request reprint Helix packing in the lactose permease of Escherichia coli: localization of helix VI
    L Guan
    Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA 90095 1662, USA
    J Mol Biol 312:69-77. 2001
    ....
  33. ncbi request reprint The C-4 hydroxyl group of galactopyranosides is the major determinant for ligand recognition by the lactose permease of Escherichia coli
    M Sahin-Toth
    Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, California 90095 1662, USA
    Biochemistry 40:13015-9. 2001
    ..Moreover, the C-4 hydroxyl is identified as the major determinant of ligand binding, suggesting that sugar recognition in lactose permease may have evolved to discriminate primarily between gluco- and galactopyranosides...
  34. pmc Functional complementation of internal deletion mutants in the lactose permease of Escherichia coli
    E Bibi
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90024 1574
    Proc Natl Acad Sci U S A 89:1524-8. 1992
    ....
  35. pmc Functional interactions between putative intramembrane charged residues in the lactose permease of Escherichia coli
    M Sahin-Toth
    Howard Hughes Medical Institute, Department of Physiology, University of California, Los Angeles 90024 1574
    Proc Natl Acad Sci U S A 89:10547-51. 1992
    ..In any event, the findings suggest that putative transmembrane helix VII lies next to helices X and XI in the tertiary structure of lactose permease...
  36. pmc Toward the bilayer proteome, electrospray ionization-mass spectrometry of large, intact transmembrane proteins
    J P Whitelegge
    Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 96:10695-8. 1999
    ..Furthermore, ESI-MS is used to titrate reactive thiols with N-ethylmaleimide. Treatment of the native protein solubilized in detergent micelles reveals only two reactive thiols, and both are protected by a substrate analog...
  37. ncbi request reprint The lac permease of Escherichia coli: a prototypic energy-transducing membrane protein
    H R Kaback
    Howard Hughes Medical Institute, University of California, Los Angeles 90024 1570
    Biochim Biophys Acta 1018:160-2. 1990
  38. ncbi request reprint Isolation and functional reconstitution of soluble melibiose permease from Escherichia coli
    P D Roepe
    Howard Hughes Medical Institute, University of California, Los Angeles 90024 1574
    Biochemistry 29:2572-7. 1990
    ....
  39. pmc Fourier transform infrared spectroscopy reveals a rigid alpha-helical assembly for the tetrameric Streptomyces lividans K+ channel
    J le Coutre
    Howard Hughes Medical Institute, Departments of Physiology and Microbiology and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles, CA 90095 1662, USA
    Proc Natl Acad Sci U S A 95:6114-7. 1998
    ..On average, the alpha-helices are tilted 33 degrees normal to the membrane surface. The results are discussed in relationship to the lactose permease of Escherichia coli, a membrane transport protein...
  40. ncbi request reprint Membrane topology of the melibiose permease of Escherichia coli studied by melB-phoA fusion analysis
    T Pourcher
    Laboratoire J Maetz, D├ępartement de Biologie Cellulaire et Mol├ęculaire CEA, France
    Biochemistry 35:4161-8. 1996
    ....
  41. ncbi request reprint Engineering the lac permease for purification and crystallization
    G G Prive
    Ontario Cancer Institute, University of Toronto, Canada
    J Bioenerg Biomembr 28:29-34. 1996
    ..The "red permease" is very easy to monitor through the steps of expression, purification, concentration, and crystallization...
  42. pmc Deduction of consensus binding sequences on proteins that bind IIAGlc of the phosphoenolpyruvate:sugar phosphotransferase system by cysteine scanning mutagenesis of Escherichia coli lactose permease
    M Sondej
    Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 96:3525-30. 1999
    ..The requirement for two interaction regions is interpreted in the regulatory framework of a substrate-dependent conformational change that brings those two regions into an orientation optimal for binding IIAGlc...
  43. pmc Topology of allosteric regulation of lactose permease
    Y J Seok
    Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, Bethesda, MD 20892 4036, USA
    Proc Natl Acad Sci U S A 94:13515-9. 1997
    ..A topological map of the proposed interaction is presented...
  44. ncbi request reprint Cloning and functional expression in bacteria of a novel glucose transporter present in liver, intestine, kidney, and beta-pancreatic islet cells
    B Thorens
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142
    Cell 55:281-90. 1988
    ..Insulinoma cells express, inappropriately, the erythrocyte glucose transporter, and we suggest that this may be related to their inability to secrete insulin in response to elevations in glucose...
  45. pmc Vinylglycolate resistance in Escherichia coli
    L Shaw
    J Bacteriol 121:1047-55. 1975
    ..This indicates that vinylglycolate is oxidized to 2-keto-3-butenoate before inactivating the phosphoenolpyruvate-dependent phosphotransferase system. These results were found in whole cells and confirmed in isolated membrane vesicles...