Research Topics
| ALAN SENIORSummaryAffiliation: University of Rochester Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Rate acceleration of ATP hydrolysis by F(1)F(o)-ATP synthaseA 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...- ATP synthase: motoring to the finish lineAlan E Senior
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
Cell 130:220-1. 2007.... - The catalytic transition state in ATP synthaseA 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... - The molecular mechanism of ATP synthesis by F1F0-ATP synthaseAlan 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... - Modulation of charge in the phosphate binding site of Escherichia coli ATP synthaseZulfiqar 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... - Role of betaAsn-243 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F(1)-ATPaseZulfiqar 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... - Mutagenesis of residue betaArg-246 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F1-ATPaseZulfiqar 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... - Involvement of ATP synthase residues alphaArg-376, betaArg-182, and betaLys-155 in Pi bindingZulfiqar 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... - Synergy between conserved ABC signature Ser residues in P-glycoprotein catalysisGregory 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... - Properties of P-glycoprotein with mutations in the "catalytic carboxylate" glutamate residuesGregory Tombline
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 279:46518-26. 2004.... - Inhibition of the ATPase activity of Escherichia coli ATP synthase by magnesium fluorideZulfiqar 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... - Combined mutation of catalytic glutamate residues in the two nucleotide binding domains of P-glycoprotein generates a conformation that binds ATP and ADP tightlyGregory 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... - Identification of phosphate binding residues of Escherichia coli ATP synthaseZulfiqar 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... - Cysteine-reactive fluorescence probes of catalytic sites of ATP synthaseJoachim 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... - ATP synthesis driven by proton transport in F1F0-ATP synthaseJoachim 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... - The occluded nucleotide conformation of p-glycoproteinGregory 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.... - Identification of the F1-binding surface on the delta-subunit of ATP synthaseJoachim 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... - F1F0-ATP synthase. Binding of delta subunit to a 22-residue peptide mimicking the N-terminal region of alpha subunitJoachim 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... - P-glycoprotein catalytic mechanism: studies of the ADP-vanadate inhibited stateIna L Urbatsch
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 278:23171-9. 2003.... - Quantitative determination of binding affinity of delta-subunit in Escherichia coli F1-ATPase: effects of mutation, Mg2+, and pH on KdJoachim 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... - 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 alphaAlan 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... - Involvement of the "occluded nucleotide conformation" of P-glycoprotein in the catalytic pathwayGregory 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... - Expression, purification, and characterization of cysteine-free mouse P-glycoproteinGregory 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... - Projection structure of P-glycoprotein by electron microscopy. Evidence for a closed conformation of the nucleotide binding domainsJyh-Yeuan Lee
University of California, Riverside, Department of Biochemistry, Riverside, California 92521, USA
J Biol Chem 277:40125-31. 2002.... - Analysis of sequence determinants of F1Fo-ATP synthase in the N-terminal region of alpha subunit for binding of delta subunitJoachim 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... - Quantitative determination of direct binding of b subunit to F1 in Escherichia coli F1F0-ATP synthaseJoachim 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... - Nucleotide-induced structural changes in P-glycoprotein observed by electron microscopyJyh 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... - Happy motoring with ATP synthaseAlan E Senior
Nat Struct Mol Biol 11:110-2. 2004 - Nucleotide binding to the multidrug resistance P-glycoprotein as studied by ESR spectroscopySabine 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... - Structural characterization of the interaction of the delta and alpha subunits of the Escherichia coli F1F0-ATP synthase by NMR spectroscopyStephan 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... - Fluorescent probes applied to catalytic cooperativity in ATP synthaseJoachim Weber
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
Methods Enzymol 380:132-52. 2004 - 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...
Research Grants
- BIOCHEMICAL INVESTIGATION OF P GLYCOPROTEINALAN 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 ..
- BIOCHEMICAL INVESTIGATION OF P-GLYCOPROTEINALAN 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. ..
- CHARACTERIZATION OF E.COLI F1FO-ATP SYNTHASEALAN 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. ..
- CHARACTERIZATION OF THE F1-SECTOR OF E COLI H+-ATPASEALAN 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...
- TIGHTLY-BOUND NUCLEOTIDES AND MG IN THE PROTON-ATPASEALAN 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...
- FASEB SUMMER RESEARCH CONFERENCE: TRANSPORT ATPASESALAN SENIOR; Fiscal Year: 2005..This conference, focussed on transport ATPases but multidisciplinary in nature, is therefore very clearly related to the mission of NIH. ..