ALAN SENIOR

Summary

Affiliation: University of Rochester
Country: USA

Publications

  1. pmc Two ATPases
    Alan E Senior
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
    J Biol Chem 287:30049-62. 2012
  2. ncbi request reprint ATP synthase: motoring to the finish line
    Alan E Senior
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
    Cell 130:220-1. 2007
  3. ncbi request reprint The catalytic transition state in ATP synthase
    A E Senior
    Department of Biochemistry and Biophysics, Box 712, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Bioenerg Biomembr 32:523-9. 2000
  4. ncbi request reprint The molecular mechanism of ATP synthesis by F1F0-ATP synthase
    Alan E Senior
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Box 712, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Biochim Biophys Acta 1553:188-211. 2002
  5. ncbi request reprint Rate acceleration of ATP hydrolysis by F(1)F(o)-ATP synthase
    A E Senior
    Department of Biochemistry, University of Rochester Medical Center, Rochester, NY 14642, USA
    J Exp Biol 203:35-40. 2000
  6. ncbi request reprint Role of betaAsn-243 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F(1)-ATPase
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:46057-64. 2004
  7. ncbi request reprint Mutagenesis of residue betaArg-246 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F1-ATPase
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:31505-13. 2004
  8. ncbi request reprint Modulation of charge in the phosphate binding site of Escherichia coli ATP synthase
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 280:27981-9. 2005
  9. ncbi request reprint Involvement of ATP synthase residues alphaArg-376, betaArg-182, and betaLys-155 in Pi binding
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, Box 712, University of Rochester Medical Center, Rochester, NY 14642, USA
    FEBS Lett 579:523-8. 2005
  10. ncbi request reprint Synergy between conserved ABC signature Ser residues in P-glycoprotein catalysis
    Gregory Tombline
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:5363-73. 2004

Research Grants

Collaborators

Detail Information

Publications33

  1. pmc Two ATPases
    Alan E Senior
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
    J Biol Chem 287:30049-62. 2012
    ..Purification of the protein in large quantity allowed detailed characterization of catalysis, formulation of an alternating sites mechanism, and recently, advances in structural characterization...
  2. ncbi request reprint ATP synthase: motoring to the finish line
    Alan E Senior
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
    Cell 130:220-1. 2007
    ....
  3. ncbi request reprint The catalytic transition state in ATP synthase
    A E Senior
    Department of Biochemistry and Biophysics, Box 712, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Bioenerg Biomembr 32:523-9. 2000
    ..We speculate that formation and collapse of the transition state may engender catalytic site alpha/beta subunit-interface conformational movement, which is linked to gamma-subunit rotation...
  4. ncbi request reprint The molecular mechanism of ATP synthesis by F1F0-ATP synthase
    Alan E Senior
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Box 712, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Biochim Biophys Acta 1553:188-211. 2002
    ..In this review we summarize current state of knowledge and present a hypothesis for the molecular mechanism of ATP synthesis...
  5. ncbi request reprint Rate acceleration of ATP hydrolysis by F(1)F(o)-ATP synthase
    A E Senior
    Department of Biochemistry, University of Rochester Medical Center, Rochester, NY 14642, USA
    J Exp Biol 203:35-40. 2000
    ..Fifth, there is strong positive catalytic cooperativity, with binding of MgATP at all three sites yielding the maximum rate (V(max)); the molecular basis of this factor remains to be elucidated...
  6. ncbi request reprint Role of betaAsn-243 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F(1)-ATPase
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:46057-64. 2004
    ..It is also probably involved in orientation of the "attacking water" and of an associated second water...
  7. ncbi request reprint Mutagenesis of residue betaArg-246 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F1-ATPase
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:31505-13. 2004
    ..Phosphate protected against NBD-Cl inhibition in wild type but not in mutants. The results show that phosphate can bind in the betaE catalytic site of E. coli F(1) and that betaArg-246 is an important phosphate-binding residue...
  8. ncbi request reprint Modulation of charge in the phosphate binding site of Escherichia coli ATP synthase
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 280:27981-9. 2005
    ..However, since none of the mutants showed significant function in growth tests, ATP-driven proton pumping, or ATPase activity assays, it is apparent that specific stereochemical interactions of catalytic site Arg residues are paramount...
  9. ncbi request reprint Involvement of ATP synthase residues alphaArg-376, betaArg-182, and betaLys-155 in Pi binding
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, Box 712, University of Rochester Medical Center, Rochester, NY 14642, USA
    FEBS Lett 579:523-8. 2005
    ..Therefore, in ATP synthesis initial binding of substrate Pi in open catalytic site betaE is supported by each of these three residues...
  10. ncbi request reprint Synergy between conserved ABC signature Ser residues in P-glycoprotein catalysis
    Gregory Tombline
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:5363-73. 2004
    ..Because the transition state complex is currently believed to form in the dimerized state of the nucleotide binding domains, one may also conclude that both Ser-OH are necessary for correct formation of the dimer state...
  11. ncbi request reprint Inhibition of the ATPase activity of Escherichia coli ATP synthase by magnesium fluoride
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, Box 712, University of Rochester Medical Center, Rochester, NY 14642, USA
    FEBS Lett 580:517-20. 2006
    ..The data demonstrate that MgFx in combination with MgADP behaves as a tight-binding transition state analog in E. coli ATP synthase...
  12. ncbi request reprint Identification of phosphate binding residues of Escherichia coli ATP synthase
    Zulfiqar Ahmad
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York, USA
    J Bioenerg Biomembr 37:437-40. 2005
    ..Positive electrostatic charge in the vicinity of betaArg-246 is shown to be one important component of Pi binding...
  13. ncbi request reprint Properties of P-glycoprotein with mutations in the "catalytic carboxylate" glutamate residues
    Gregory Tombline
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:46518-26. 2004
    ....
  14. ncbi request reprint Cysteine-reactive fluorescence probes of catalytic sites of ATP synthase
    Joachim Weber
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    Arch Biochem Biophys 397:1-10. 2002
    ..The signal of the latter responds differentially to nucleoside diphosphate versus triphosphate bound in catalytic sites...
  15. ncbi request reprint Combined mutation of catalytic glutamate residues in the two nucleotide binding domains of P-glycoprotein generates a conformation that binds ATP and ADP tightly
    Gregory Tombline
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:31212-20. 2004
    ..We envisage that in wild-type the occluded nucleotide conformation occurs transiently after MgATP binds to both NBDs with associated dimerization, and before progression to the transition state...
  16. ncbi request reprint ATP synthesis driven by proton transport in F1F0-ATP synthase
    Joachim Weber
    Department of Biochemistry and Biophysics, Box 712, University of Rochester Medical Center, Rochester, NY 14642, USA
    FEBS Lett 545:61-70. 2003
    ..Here we review the most recent work on rapidly developing areas within the field and present proposals for enzymatic and mechanoenzymatic mechanisms...
  17. ncbi request reprint F1F0-ATP synthase. Binding of delta subunit to a 22-residue peptide mimicking the N-terminal region of alpha subunit
    Joachim Weber
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, New York 14642, USA
    J Biol Chem 278:13623-6. 2003
    ..Hypothetically a helical region of residues alpha N1-22 packs with helices 1 and 5 on the F(1)-binding face of delta, forming the alpha/delta interface...
  18. ncbi request reprint Involvement of the "occluded nucleotide conformation" of P-glycoprotein in the catalytic pathway
    Gregory Tombline
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Box 712 Rochester, New York 14642, USA
    Biochemistry 44:12879-86. 2005
    ..The pathway progresses such that the tightly bound MgATP enters the transition state and is hydrolyzed. This work suggests that small molecules or peptides that interact at the NBD dimer interface might effectively disable Pgp catalysis...
  19. ncbi request reprint The occluded nucleotide conformation of p-glycoprotein
    Gregory Tombline
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Box 712, Rochester, New York 14642, USA
    J Bioenerg Biomembr 37:497-500. 2005
    ....
  20. ncbi request reprint P-glycoprotein catalytic mechanism: studies of the ADP-vanadate inhibited state
    Ina L Urbatsch
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 278:23171-9. 2003
    ....
  21. pmc Assembly of the stator in Escherichia coli ATP synthase. Complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha
    Alan E Senior
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA alan_senior urmc rochester edu
    Biochemistry 45:15893-902. 2006
    ..The cytoplasmic fragment of the b subunit (bsol) did not bind to isolated alpha. It might also be that complexation of alpha with beta subunits is prerequisite for direct binding of stator b subunit to the F1-sector...
  22. ncbi request reprint Identification of the F1-binding surface on the delta-subunit of ATP synthase
    Joachim Weber
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 278:13409-16. 2003
    ..The new data show that the stator is "overengineered" to resist rotor torque during catalysis...
  23. ncbi request reprint Quantitative determination of binding affinity of delta-subunit in Escherichia coli F1-ATPase: effects of mutation, Mg2+, and pH on Kd
    Joachim Weber
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 277:18390-6. 2002
    ..High pH environment greatly reduced delta binding affinity, suggesting the involvement of protonatable side-chains in the binding site...
  24. ncbi request reprint Nucleotide-induced structural changes in P-glycoprotein observed by electron microscopy
    Jyh Yeuan Lee
    Department of Biochemistry, University of California, Riverside, California 92521, USA
    J Biol Chem 283:5769-79. 2008
    ..The structural analysis presented here adds to the emerging picture that multidrug ABC transporters function by switching between two major conformations in a nucleotide-dependent manner...
  25. ncbi request reprint Analysis of sequence determinants of F1Fo-ATP synthase in the N-terminal region of alpha subunit for binding of delta subunit
    Joachim Weber
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:25673-9. 2004
    ..The potential capping box sequence per se appeared less important. Impairment of alpha/delta binding brings about functional impairment due to reduced level of assembly of ATP synthase in cells...
  26. ncbi request reprint Expression, purification, and characterization of cysteine-free mouse P-glycoprotein
    Gregory Tombline
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
    Arch Biochem Biophys 445:124-8. 2006
    ..The results also support our previous conclusion that both catalytic sites must be intact for normal function in Pgp...
  27. ncbi request reprint Quantitative determination of direct binding of b subunit to F1 in Escherichia coli F1F0-ATP synthase
    Joachim Weber
    Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:11253-8. 2004
    ..36 microm in EDTA buffer. This work demonstrates quantitatively how binding of the cytoplasmic portion of the b subunit directly to F(1) contributes to stator resistance and emphasizes the importance of Mg(2+) in stator interactions...
  28. ncbi request reprint Projection structure of P-glycoprotein by electron microscopy. Evidence for a closed conformation of the nucleotide binding domains
    Jyh Yeuan Lee
    University of California, Riverside, Department of Biochemistry, Riverside, California 92521, USA
    J Biol Chem 277:40125-31. 2002
    ....
  29. ncbi request reprint Happy motoring with ATP synthase
    Alan E Senior
    Nat Struct Mol Biol 11:110-2. 2004
  30. ncbi request reprint Nucleotide binding to the multidrug resistance P-glycoprotein as studied by ESR spectroscopy
    Sabine Delannoy
    Department of Biological Sciences, Southern Methodist University, Dallas, Texas 75275, USA
    Biochemistry 44:14010-9. 2005
    ..The study shows that SL-ATP is an excellent substrate analogue that will allow further exploration of structure and dynamics within the nucleotide binding domains of this important enzyme...
  31. ncbi request reprint Structural characterization of the interaction of the delta and alpha subunits of the Escherichia coli F1F0-ATP synthase by NMR spectroscopy
    Stephan Wilkens
    Departments of Biochemistry, University of California at Riverside, Riverside, California 92521, USA
    Biochemistry 44:11786-94. 2005
    ..On the basis of intermolecular contacts observed in (12)C/(13)C-filtered NOESY experiments, we describe structural details of the interaction of the delta-subunit N-terminal domain with the alpha-subunit N-terminal alpha helix...
  32. ncbi request reprint Mutational analysis of conserved aromatic residues in the A-loop of the ABC transporter ABCB1A (mouse Mdr3)
    Isabelle Carrier
    Department of Biochemistry and McGill Cancer Centre, McGill University, McIntyre Medical Sciences Building, Room 907, 3655 Sir William Osler Drive, Montreal, Que, Canada H3G 1Y6
    FEBS Lett 581:301-8. 2007
    ..On the other hand, Y397W and Y1040W showed impaired transport and greatly reduced ATPase activity, including a approximately 10-fold increase in Km for MgATP. Thus, Y397 and Y1040 play an important role in Abcb1a catalysis...
  33. ncbi request reprint Fluorescent probes applied to catalytic cooperativity in ATP synthase
    Joachim Weber
    Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
    Methods Enzymol 380:132-52. 2004

Research Grants29

  1. BIOCHEMICAL INVESTIGATION OF P GLYCOPROTEIN
    ALAN SENIOR; Fiscal Year: 2000
    ..Basic knowledge of this kind will be invaluable in devising ways to disable P-glycoprotein in cells and overcome multidrig resistanmce in patients ..
  2. BIOCHEMICAL INVESTIGATION OF P-GLYCOPROTEIN
    ALAN SENIOR; Fiscal Year: 2004
    ..Basic knowledge of this kind will be invaluable in devising ways to disable P-glycoprotein and overcome drug-resistance in patients. ..
  3. CHARACTERIZATION OF E.COLI F1FO-ATP SYNTHASE
    ALAN SENIOR; Fiscal Year: 2004
    ..ATP-driven pumps are very widely distributed in nature, and are involved in many disease states. Work to be done here will consequently have broad impact in biology and medicine. ..
  4. CHARACTERIZATION OF THE F1-SECTOR OF E COLI H+-ATPASE
    ALAN SENIOR; Fiscal Year: 1990
    ..The nature of energy-coupling and catalysis in ion-transporting ATPases is a fundamental problem of biology. The long-term goal of this proposal is to deduce molecular insights into this problem...
  5. TIGHTLY-BOUND NUCLEOTIDES AND MG IN THE PROTON-ATPASE
    ALAN SENIOR; Fiscal Year: 1980
    ..This is the most complex enzyme known, and its function is of topical importance since it converts chemical and electrical energy at high efficiency at ordinary temperatures...
  6. FASEB SUMMER RESEARCH CONFERENCE: TRANSPORT ATPASES
    ALAN SENIOR; Fiscal Year: 2005
    ..This conference, focussed on transport ATPases but multidisciplinary in nature, is therefore very clearly related to the mission of NIH. ..