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Alan Senior

TitleProfessor Emeritus
InstitutionSchool of Medicine and Dentistry
DepartmentBiochemistry and Biophysics
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester NY 14642
 
 Overview
Multi drug resistance in cancer; ATP synthesis in bacteria and mitochondria.

(1) Multidrug resistance in cancer. Cancer chemotherapy often fails because the tumor develops resistance to multiple drugs simultaneously. The culprit is multidrug-resistance protein (mdr) also known as P-glycoprotein. It is located in plasma membranes, and uses ATP to transport drugs out of cells. We have generated a cell line which greatly overexpresses mdr, from which enriched plasma membranes and purified protein are readily obtained. The long-term goal is to learn ways to disable or circumvent mdr protein in cancer cells.

(2) ATP synthesis and hydrolysis in F1Fo-ATP synthase. ATP synthase is the smallest known rotary motor. It uses subunit rotation to drive ATP synthesis, and ATP hydrolysis to drive subunit rotation. The subunit rotation is linked in turn to utilization or generation of a membrane proton gradient. We are using a variety of probes to study the mechanism of catalysis and to elucidate the molecular linkage between catalysis and subunit rotation. We use the E. coli enzyme and a range of molecular genetics, biochemical and biophysical techniques. In recent work we have focussed on application of fluoroscent probes of cataytic sites which have yielded rapid and sensitive information about mechanism.

 
 Selected Publications
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  1. Senior AE. Two ATPases. J Biol Chem. 2012 Aug 31; 287(36):30049-62.
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  2. Senior AE. Reaction chemistry ABC-style. Proc Natl Acad Sci U S A. 2011 Sep 13; 108(37):15015-6.
    View in: PubMed
  3. Li W, Brudecki LE, Senior AE, Ahmad Z. Role of {alpha}-subunit VISIT-DG sequence residues Ser-347 and Gly-351 in the catalytic sites of Escherichia coli ATP synthase. J Biol Chem. 2009 Apr 17; 284(16):10747-54.
    View in: PubMed
  4. Lee JY, Urbatsch IL, Senior AE, Wilkens S. Nucleotide-induced structural changes in P-glycoprotein observed by electron microscopy. J Biol Chem. 2008 Feb 29; 283(9):5769-79.
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  5. Senior AE. ATP synthase: motoring to the finish line. Cell. 2007 Jul 27; 130(2):220-1.
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  6. Carrier I, Urbatsch IL, Senior AE, Gros P. Mutational analysis of conserved aromatic residues in the A-loop of the ABC transporter ABCB1A (mouse Mdr3). FEBS Lett. 2007 Jan 23; 581(2):301-8.
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  7. Senior AE, Muharemagic A, Wilke-Mounts S. 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. Biochemistry. 2006 Dec 26; 45(51):15893-902.
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  8. Ahmad Z, Senior AE. Inhibition of the ATPase activity of Escherichia coli ATP synthase by magnesium fluoride. FEBS Lett. 2006 Jan 23; 580(2):517-20.
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  9. Ahmad Z, Senior AE. Identification of phosphate binding residues of Escherichia coli ATP synthase. J Bioenerg Biomembr. 2005 Dec; 37(6):437-40.
    View in: PubMed
  10. Tombline G, Senior AE. The occluded nucleotide conformation of p-glycoprotein. J Bioenerg Biomembr. 2005 Dec; 37(6):497-500.
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  11. Tombline G, Urbatsch IL, Virk N, Muharemagic A, White LB, Senior AE. Expression, purification, and characterization of cysteine-free mouse P-glycoprotein. Arch Biochem Biophys. 2006 Jan 1; 445(1):124-8.
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  12. Delannoy S, Urbatsch IL, Tombline G, Senior AE, Vogel PD. Nucleotide binding to the multidrug resistance P-glycoprotein as studied by ESR spectroscopy. Biochemistry. 2005 Oct 25; 44(42):14010-9.
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  13. Tombline G, Muharemagic A, White LB, Senior AE. Involvement of the "occluded nucleotide conformation" of P-glycoprotein in the catalytic pathway. Biochemistry. 2005 Sep 27; 44(38):12879-86.
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  14. Wilkens S, Borchardt D, Weber J, Senior AE. Structural characterization of the interaction of the delta and alpha subunits of the Escherichia coli F1F0-ATP synthase by NMR spectroscopy. Biochemistry. 2005 Sep 6; 44(35):11786-94.
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  15. Ahmad Z, Senior AE. Modulation of charge in the phosphate binding site of Escherichia coli ATP synthase. J Biol Chem. 2005 Jul 29; 280(30):27981-9.
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  16. Ahmad Z, Senior AE. Involvement of ATP synthase residues alphaArg-376, betaArg-182, and betaLys-155 in Pi binding. FEBS Lett. 2005 Jan 17; 579(2):523-8.
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  17. Tombline G, Bartholomew LA, Tyndall GA, Gimi K, Urbatsch IL, Senior AE. Properties of P-glycoprotein with mutations in the "catalytic carboxylate" glutamate residues. J Biol Chem. 2004 Nov 5; 279(45):46518-26.
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  18. Ahmad Z, Senior AE. Role of betaAsn-243 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F(1)-ATPase. J Biol Chem. 2004 Oct 29; 279(44):46057-64.
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  19. Tombline G, Bartholomew LA, Urbatsch IL, Senior AE. Combined mutation of catalytic glutamate residues in the two nucleotide binding domains of P-glycoprotein generates a conformation that binds ATP and ADP tightly. J Biol Chem. 2004 Jul 23; 279(30):31212-20.
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  20. Ahmad Z, Senior AE. Mutagenesis of residue betaArg-246 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F1-ATPase. J Biol Chem. 2004 Jul 23; 279(30):31505-13.
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  21. Weber J, Muharemagic A, Wilke-Mounts S, Senior AE. Analysis of sequence determinants of F1Fo-ATP synthase in the N-terminal region of alpha subunit for binding of delta subunit. J Biol Chem. 2004 Jun 11; 279(24):25673-9.
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  22. Senior AE, Weber J. Happy motoring with ATP synthase. Nat Struct Mol Biol. 2004 Feb; 11(2):110-2.
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  23. Weber J, Wilke-Mounts S, Nadanaciva S, Senior AE. Quantitative determination of direct binding of b subunit to F1 in Escherichia coli F1F0-ATP synthase. J Biol Chem. 2004 Mar 19; 279(12):11253-8.
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  24. Weber J, Senior AE. Fluorescent probes applied to catalytic cooperativity in ATP synthase. Methods Enzymol. 2004; 380:132-52.
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  25. Tombline G, Bartholomew L, Gimi K, Tyndall GA, Senior AE. Synergy between conserved ABC signature Ser residues in P-glycoprotein catalysis. J Biol Chem. 2004 Feb 13; 279(7):5363-73.
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  26. Weber J, Senior AE. ATP synthesis driven by proton transport in F1F0-ATP synthase. FEBS Lett. 2003 Jun 12; 545(1):61-70.
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  27. Urbatsch IL, Tyndall GA, Tombline G, Senior AE. P-glycoprotein catalytic mechanism: studies of the ADP-vanadate inhibited state. J Biol Chem. 2003 Jun 20; 278(25):23171-9.
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  28. Weber J, Muharemagic A, Wilke-Mounts S, Senior AE. F1F0-ATP synthase. Binding of delta subunit to a 22-residue peptide mimicking the N-terminal region of alpha subunit. J Biol Chem. 2003 Apr 18; 278(16):13623-6.
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  29. Weber J, Wilke-Mounts S, Senior AE. Identification of the F1-binding surface on the delta-subunit of ATP synthase. J Biol Chem. 2003 Apr 11; 278(15):13409-16.
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  30. Lee JY, Urbatsch IL, Senior AE, Wilkens S. Projection structure of P-glycoprotein by electron microscopy. Evidence for a closed conformation of the nucleotide binding domains. J Biol Chem. 2002 Oct 18; 277(42):40125-31.
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  31. Weber J, Wilke-Mounts S, Senior AE. Quantitative determination of binding affinity of delta-subunit in Escherichia coli F1-ATPase: effects of mutation, Mg2+, and pH on Kd. J Biol Chem. 2002 May 24; 277(21):18390-6.
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  32. Senior AE, Nadanaciva S, Weber J. The molecular mechanism of ATP synthesis by F1F0-ATP synthase. Biochim Biophys Acta. 2002 Feb 15; 1553(3):188-211.
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  33. Weber J, Bijol V, Wilke-Mounts S, Senior AE. Cysteine-reactive fluorescence probes of catalytic sites of ATP synthase. Arch Biochem Biophys. 2002 Jan 1; 397(1):1-10.
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  34. Weber J, Senior AE. Bi-site catalysis in F1-ATPase: does it exist? J Biol Chem. 2001 Sep 21; 276(38):35422-8.
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  35. Urbatsch IL, Gimi K, Wilke-Mounts S, Lerner-Marmarosh N, Rousseau ME, Gros P, Senior AE. Cysteines 431 and 1074 are responsible for inhibitory disulfide cross-linking between the two nucleotide-binding sites in human P-glycoprotein. J Biol Chem. 2001 Jul 20; 276(29):26980-7.
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  36. Urbatsch IL, Wilke-Mounts S, Gimi K, Senior AE. Purification and characterization of N-glycosylation mutant mouse and human P-glycoproteins expressed in Pichia pastoris cells. Arch Biochem Biophys. 2001 Apr 1; 388(1):171-7.
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  37. Weber J, Nadanaciva S, Senior AE. ATP-driven rotation of the gamma subunit in F(1)-ATPase. FEBS Lett. 2000 Oct 13; 483(1):1-5.
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  38. Urbatsch IL, Gimi K, Wilke-Mounts S, Senior AE. Investigation of the role of glutamine-471 and glutamine-1114 in the two catalytic sites of P-glycoprotein. Biochemistry. 2000 Oct 3; 39(39):11921-7.
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  39. Senior AE, Weber J, Nadanaciva S. The catalytic transition state in ATP synthase. J Bioenerg Biomembr. 2000 Oct; 32(5):523-9.
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  40. Urbatsch IL, Gimi K, Wilke-Mounts S, Senior AE. Conserved walker A Ser residues in the catalytic sites of P-glycoprotein are critical for catalysis and involved primarily at the transition state step. J Biol Chem. 2000 Aug 11; 275(32):25031-8.
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  41. Nadanaciva S, Weber J, Senior AE. New probes of the F1-ATPase catalytic transition state reveal that two of the three catalytic sites can assume a transition state conformation simultaneously. Biochemistry. 2000 Aug 8; 39(31):9583-90.
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  42. Kwan T, Loughrey H, Brault M, Gruenheid S, Urbatsch IL, Senior AE, Gros P. Functional analysis of a tryptophan-less P-glycoprotein: a tool for tryptophan insertion and fluorescence spectroscopy. Mol Pharmacol. 2000 Jul; 58(1):37-47.
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  43. Weber J, Senior AE. ATP synthase: what we know about ATP hydrolysis and what we do not know about ATP synthesis. Biochim Biophys Acta. 2000 May 31; 1458(2-3):300-9.
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  44. Weber J, Senior AE. Features of F(1)-ATPase catalytic and noncatalytic sites revealed by fluorescence lifetimes and acrylamide quenching of specifically inserted tryptophan residues. Biochemistry. 2000 May 9; 39(18):5287-94.
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  45. Senior AE, Nadanaciva S, Weber J. Rate acceleration of ATP hydrolysis by F(1)F(o)-ATP synthase. J Exp Biol. 2000 Jan; 203(Pt 1):35-40.
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  46. Lerner-Marmarosh N, Gimi K, Urbatsch IL, Gros P, Senior AE. Large scale purification of detergent-soluble P-glycoprotein from Pichia pastoris cells and characterization of nucleotide binding properties of wild-type, Walker A, and Walker B mutant proteins. J Biol Chem. 1999 Dec 3; 274(49):34711-8.
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  47. Nadanaciva S, Weber J, Wilke-Mounts S, Senior AE. Importance of F1-ATPase residue alpha-Arg-376 for catalytic transition state stabilization. Biochemistry. 1999 Nov 23; 38(47):15493-9.
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  48. Weber J, Dunn SD, Senior AE. Effect of the epsilon-subunit on nucleotide binding to Escherichia coli F1-ATPase catalytic sites. J Biol Chem. 1999 Jul 2; 274(27):19124-8.
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  49. Nadanaciva S, Weber J, Senior AE. The role of beta-Arg-182, an essential catalytic site residue in Escherichia coli F1-ATPase. Biochemistry. 1999 Jun 15; 38(24):7670-7.
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  50. Nadanaciva S, Weber J, Senior AE. Binding of the transition state analog MgADP-fluoroaluminate to F1-ATPase. J Biol Chem. 1999 Mar 12; 274(11):7052-8.
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  51. Weber J, Senior AE. Effects of the inhibitors azide, dicyclohexylcarbodiimide, and aurovertin on nucleotide binding to the three F1-ATPase catalytic sites measured using specific tryptophan probes. J Biol Chem. 1998 Dec 11; 273(50):33210-5.
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  52. Weber J, Wilke-Mounts S, Hammond ST, Senior AE. Tryptophan substitutions surrounding the nucleotide in catalytic sites of F1-ATPase. Biochemistry. 1998 Sep 1; 37(35):12042-50.
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  53. Senior AE, Gros P, Urbatsch IL. Residues in P-glycoprotein catalytic sites that react with the inhibitor 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. Arch Biochem Biophys. 1998 Sep 1; 357(1):121-5.
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  54. Senior AE. Catalytic mechanism of P-glycoprotein. Acta Physiol Scand Suppl. 1998 Aug; 643:213-8.
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  55. Löbau S, Weber J, Senior AE. Catalytic site nucleotide binding and hydrolysis in F1F0-ATP synthase. Biochemistry. 1998 Jul 28; 37(30):10846-53.
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  56. Rebbeor JF, Senior AE. Effects of cardiovascular drugs on ATPase activity of P-glycoprotein in plasma membranes and in purified reconstituted form. Biochim Biophys Acta. 1998 Feb 2; 1369(1):85-93.
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  57. Senior AE, Bhagat S. P-glycoprotein shows strong catalytic cooperativity between the two nucleotide sites. Biochemistry. 1998 Jan 20; 37(3):831-6.
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  58. Weber J, Hammond ST, Wilke-Mounts S, Senior AE. Mg2+ coordination in catalytic sites of F1-ATPase. Biochemistry. 1998 Jan 13; 37(2):608-14.
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  59. Senior AE, al-Shawi MK, Urbatsch IL. ATPase activity of Chinese hamster P-glycoprotein. Methods Enzymol. 1998; 292:514-23.
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  60. Sankaran B, Bhagat S, Senior AE. Photoaffinity labelling of P-glycoprotein catalytic sites. FEBS Lett. 1997 Nov 3; 417(1):119-22.
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  61. Weber J, Senior AE. Binding of TNP-ATP and TNP-ADP to the non-catalytic sites of Escherichia coli F1-ATPase. FEBS Lett. 1997 Jul 21; 412(1):169-72.
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  62. Sankaran B, Bhagat S, Senior AE. Inhibition of P-glycoprotein ATPase activity by beryllium fluoride. Biochemistry. 1997 Jun 3; 36(22):6847-53.
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  63. Senior AE, Gadsby DC. ATP hydrolysis cycles and mechanism in P-glycoprotein and CFTR. Semin Cancer Biol. 1997 Jun; 8(3):143-50.
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  64. Sankaran B, Bhagat S, Senior AE. Inhibition of P-glycoprotein ATPase activity by procedures involving trapping of nucleotide in catalytic sites. Arch Biochem Biophys. 1997 May 1; 341(1):160-9.
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  65. Weber J, Senior AE. Catalytic mechanism of F1-ATPase. Biochim Biophys Acta. 1997 Mar 28; 1319(1):19-58.
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  66. Löbau S, Weber J, Senior AE. Nucleotide occupancy of F1-ATPase catalytic sites under crystallization conditions. FEBS Lett. 1997 Mar 3; 404(1):15-8.
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  67. Löbau S, Weber J, Wilke-Mounts S, Senior AE. F1-ATPase, roles of three catalytic site residues. J Biol Chem. 1997 Feb 7; 272(6):3648-56.
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  68. Weber J, Bowman C, Senior AE. Specific tryptophan substitution in catalytic sites of Escherichia coli F1-ATPase allows differentiation between bound substrate ATP and product ADP in steady-state catalysis. J Biol Chem. 1996 Aug 2; 271(31):18711-8.
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  69. Weber J, Senior AE. F1F0-ATP synthase: development of direct optical probes of the catalytic mechanism. Biochim Biophys Acta. 1996 Jul 18; 1275(1-2):101-4.
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  70. Weber J, Senior AE. Binding and hydrolysis of TNP-ATP by Escherichia coli F1-ATPase. J Biol Chem. 1996 Feb 16; 271(7):3474-7.
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  71. Senior AE, al-Shawi MK, Urbatsch IL. The catalytic cycle of P-glycoprotein. FEBS Lett. 1995 Dec 27; 377(3):285-9.
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  72. Wilke-Mounts S, Pagan J, Senior AE. Mutagenesis and reversion analysis of residue Met-209 of the beta-subunit of Escherichia coli ATP synthase. Arch Biochem Biophys. 1995 Dec 1; 324(1):153-8.
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  73. Urbatsch IL, Sankaran B, Bhagat S, Senior AE. Both P-glycoprotein nucleotide-binding sites are catalytically active. J Biol Chem. 1995 Nov 10; 270(45):26956-61.
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  74. Senior AE, Weber J, al-Shawi MK. Catalytic mechanism of Escherichia coli F1-ATPase. Biochem Soc Trans. 1995 Nov; 23(4):747-52.
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  75. Weber J, Bowman C, Wilke-Mounts S, Senior AE. alpha-Aspartate 261 is a key residue in noncatalytic sites of Escherichia coli F1-ATPase. J Biol Chem. 1995 Sep 8; 270(36):21045-9.
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  76. Urbatsch IL, Sankaran B, Weber J, Senior AE. P-glycoprotein is stably inhibited by vanadate-induced trapping of nucleotide at a single catalytic site. J Biol Chem. 1995 Aug 18; 270(33):19383-90.
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  77. Schmidt G, Senior AE. ATP-dependent inactivation of the beta-Ser339Cys mutant F1-ATPase from Escherichia coli by N-ethylmaleimide. Biochemistry. 1995 Aug 1; 34(30):9694-9.
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  78. Weber J, Senior AE. Location and properties of pyrophosphate-binding sites in Escherichia coli F1-ATPase. J Biol Chem. 1995 May 26; 270(21):12653-8.
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  79. Gibson SL, al-Shawi MK, Senior AE, Hile R. Inhibition of the ATPase activity of P-glycoprotein by porphyrin photosensitization of multidrug-resistant cells in vitro. Photochem Photobiol. 1995 Apr; 61(4):390-6.
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  80. Senior AE, al-Shawi MK, Urbatsch IL. ATP hydrolysis by multidrug-resistance protein from Chinese hamster ovary cells. J Bioenerg Biomembr. 1995 Feb; 27(1):31-6.
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  81. Urbatsch IL, Senior AE. Effects of lipids on ATPase activity of purified Chinese hamster P-glycoprotein. Arch Biochem Biophys. 1995 Jan 10; 316(1):135-40.
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  82. Grell E, Lewitzki E, Bremer C, Kramer-Schmitt S, Weber J, Senior AE. lin-Benzo-ATP and-ADP: Versatile fluorescent probes for spectroscopic and biochemical studies. J Fluoresc. 1994 Sep; 4(3):247-50.
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  83. Weber J, Wilke-Mounts S, Senior AE. Cooperativity and stoichiometry of substrate binding to the catalytic sites of Escherichia coli F1-ATPase. Effects of magnesium, inhibitors, and mutation. J Biol Chem. 1994 Aug 12; 269(32):20462-7.
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  84. Urbatsch IL, al-Shawi MK, Senior AE. Characterization of the ATPase activity of purified Chinese hamster P-glycoprotein. Biochemistry. 1994 Jun 14; 33(23):7069-76.
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  85. Weber J, Wilke-Mounts S, Grell E, Senior AE. Tryptophan fluorescence provides a direct probe of nucleotide binding in the noncatalytic sites of Escherichia coli F1-ATPase. J Biol Chem. 1994 Apr 15; 269(15):11261-8.
    View in: PubMed
  86. al-Shawi MK, Urbatsch IL, Senior AE. Covalent inhibitors of P-glycoprotein ATPase activity. J Biol Chem. 1994 Mar 25; 269(12):8986-92.
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  87. Wilke-Mounts S, Weber J, Grell E, Senior AE. Tryptophan-free Escherichia coli F1-ATPase. Arch Biochem Biophys. 1994 Mar; 309(2):363-8.
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  88. Hazard AL, Senior AE. Mutagenesis of subunit delta from Escherichia coli F1F0-ATP synthase. J Biol Chem. 1994 Jan 7; 269(1):418-26.
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  89. Hazard AL, Senior AE. Defective energy coupling in delta-subunit mutants of Escherichia coli F1F0-ATP synthase. J Biol Chem. 1994 Jan 7; 269(1):427-32.
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  90. Weber J, Wilke-Mounts S, Lee RS, Grell E, Senior AE. Specific placement of tryptophan in the catalytic sites of Escherichia coli F1-ATPase provides a direct probe of nucleotide binding: maximal ATP hydrolysis occurs with three sites occupied. J Biol Chem. 1993 Sep 25; 268(27):20126-33.
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  91. Turina P, Aggeler R, Lee RS, Senior AE, Capaldi RA. The cysteine introduced into the alpha subunit of the Escherichia coli F1-ATPase by the mutation alpha R376C is near the alpha-beta subunit interface and close to a noncatalytic nucleotide binding site. J Biol Chem. 1993 Apr 5; 268(10):6978-84.
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  92. Senior AE, Wilke-Mounts S, al-Shawi MK. Lysine 155 in beta-subunit is a catalytic residue of Escherichia coli F1 ATPase. J Biol Chem. 1993 Apr 5; 268(10):6989-94.
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  93. Weber J, Lee RS, Wilke-Mounts S, Grell E, Senior AE. Combined application of site-directed mutagenesis, 2-azido-ATP labeling, and lin-benzo-ATP binding to study the noncatalytic sites of Escherichia coli F1-ATPase. J Biol Chem. 1993 Mar 25; 268(9):6241-7.
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  94. al-Shawi MK, Senior AE. Characterization of the adenosine triphosphatase activity of Chinese hamster P-glycoprotein. J Biol Chem. 1993 Feb 25; 268(6):4197-206.
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  95. Senior AE, al-Shawi MK. Further examination of seventeen mutations in Escherichia coli F1-ATPase beta-subunit. J Biol Chem. 1992 Oct 25; 267(30):21471-8.
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  96. Senior AE. Catalytic sites of Escherichia coli F1-ATPase. J Bioenerg Biomembr. 1992 Oct; 24(5):479-84.
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  97. Lee RS, Wilke-Mounts S, Senior AE. F1-ATPase with cysteine instead of serine at residue 373 of the alpha subunit. Arch Biochem Biophys. 1992 Sep; 297(2):334-9.
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  98. Senior AE, Lee RS, al-Shawi MK, Weber J. Catalytic properties of Escherichia coli F1-ATPase depleted of endogenous nucleotides. Arch Biochem Biophys. 1992 Sep; 297(2):340-4.
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  99. Weber J, Lee RS, Grell E, Senior AE. Investigation of the aurovertin binding site of Escherichia coli F1-ATPase by fluorescence spectroscopy and site-directed mutagenesis. Biochemistry. 1992 Jun 9; 31(22):5112-6.
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  100. al-Shawi MK, Senior AE. Catalytic sites of Escherichia coli F1-ATPase. Characterization of unisite catalysis at varied pH. Biochemistry. 1992 Jan 28; 31(3):878-85.
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  101. al-Shawi MK, Senior AE. Effects of dimethyl sulfoxide on catalysis in Escherichia coli F1-ATPase. Biochemistry. 1992 Jan 28; 31(3):886-91.
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  102. Weber J, Lee RS, Grell E, Wise JG, Senior AE. On the location and function of tyrosine beta 331 in the catalytic site of Escherichia coli F1-ATPase. J Biol Chem. 1992 Jan 25; 267(3):1712-8.
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  103. Lee RS, Pagan J, Wilke-Mounts S, Senior AE. Characterization of Escherichia coli ATP synthase beta-subunit mutations using a chromosomal deletion strain. Biochemistry. 1991 Jul 16; 30(28):6842-7.
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  104. Pagan J, Senior AE. Tight ATP and ADP binding in the noncatalytic sites of Escherichia coli F1-ATPase is not affected by mutation of bulky residues in the 'glycine-rich loop'. FEBS Lett. 1990 Oct 29; 273(1-2):147-9.
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  105. Greber UF, Senior A, Gerace L. A major glycoprotein of the nuclear pore complex is a membrane-spanning polypeptide with a large lumenal domain and a small cytoplasmic tail. EMBO J. 1990 May; 9(5):1495-502.
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  106. al-Shawi MK, Parsonage D, Senior AE. Adenosine triphosphatase and nucleotide binding activity of isolated beta-subunit preparations from Escherichia coli F1F0-ATP synthase. J Biol Chem. 1990 Apr 5; 265(10):5595-601.
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  107. al-Shawi MK, Parsonage D, Senior AE. Thermodynamic analyses of the catalytic pathway of F1-ATPase from Escherichia coli. Implications regarding the nature of energy coupling by F1-ATPases. J Biol Chem. 1990 Mar 15; 265(8):4402-10.
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  108. Pagan J, Senior AE. Mutations in alpha-subunit of Escherichia coli F1-ATPase obtained by hydroxylamine-mutagenesis of plasmids carrying the uncA gene. Arch Biochem Biophys. 1990 Mar; 277(2):283-9.
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  109. Senior AE. The proton-translocating ATPase of Escherichia coli. Annu Rev Biophys Biophys Chem. 1990; 19:7-41.
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  110. al-Shawi MK, Parsonage D, Senior AE. Kinetic characterization of the unisite catalytic pathway of seven beta-subunit mutant F1-ATPases from Escherichia coli. J Biol Chem. 1989 Sep 15; 264(26):15376-83.
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  111. Lee RS, Pagan J, Satre M, Vignais PV, Senior AE. Identification of a mutation in Escherichia coli F1-ATPase beta-subunit conferring resistance to aurovertin. FEBS Lett. 1989 Aug 14; 253(1-2):269-72.
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  112. Grubmeyer C, Skiadopoulos M, Senior AE. L-histidinol dehydrogenase, a Zn2+-metalloenzyme. Arch Biochem Biophys. 1989 Aug 1; 272(2):311-7.
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  113. Kironde FA, Parsonage D, Senior AE. Random mutagenesis of the gene for the beta-subunit of F1-ATPase from Escherichia coli. Biochem J. 1989 Apr 15; 259(2):421-6.
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  114. Al-Shawi MK, Parsonage D, Senior AE. Directed mutagenesis of the strongly conserved aspartate 242 in the beta-subunit of Escherichia coli proton-ATPase. J Biol Chem. 1988 Dec 25; 263(36):19633-9.
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  115. Al-Shawi MK, Senior AE. Complete kinetic and thermodynamic characterization of the unisite catalytic pathway of Escherichia coli F1-ATPase. Comparison with mitochondrial F1-ATPase and application to the study of mutant enzymes. J Biol Chem. 1988 Dec 25; 263(36):19640-8.
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  116. Rao R, Pagan J, Senior AE. Directed mutagenesis of the strongly conserved lysine 175 in the proposed nucleotide-binding domain of alpha-subunit from Escherichia coli F1-ATPase. J Biol Chem. 1988 Nov 5; 263(31):15957-63.
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  117. Parsonage D, Wilke-Mounts S, Senior AE. E. coli F1-ATPase: site-directed mutagenesis of the beta-subunit. FEBS Lett. 1988 May 9; 232(1):111-4.
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  118. Rao R, Al-Shawi MK, Senior AE. Trinitrophenyl-ATP and -ADP bind to a single nucleotide site on isolated beta-subunit of Escherichia coli F1-ATPase. In vitro assembly of F1-subunits requires occupancy of the nucleotide-binding site on beta-subunit by nucleoside triphosphate. J Biol Chem. 1988 Apr 25; 263(12):5569-73.
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  119. Rao R, Cunningham D, Cross RL, Senior AE. Pyridoxal 5'-diphospho-5'-adenosine binds at a single site on isolated alpha-subunit from Escherichia coli F1-ATPase and specifically reacts with lysine 201. J Biol Chem. 1988 Apr 25; 263(12):5640-5.
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  120. Maggio MB, Parsonage D, Senior AE. A mutation in the alpha-subunit of F1-ATPase from Escherichia coli affects the binding of F1 to the membrane. J Biol Chem. 1988 Apr 5; 263(10):4619-23.
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  121. Parsonage D, Al-Shawi MK, Senior AE. Directed mutations of the strongly conserved lysine 155 in the catalytic nucleotide-binding domain of beta-subunit of F1-ATPase from Escherichia coli. J Biol Chem. 1988 Apr 5; 263(10):4740-4.
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  122. Parsonage D, Wilke-Mounts S, Senior AE. Directed mutagenesis of the dicyclohexylcarbodiimide-reactive carboxyl residues in beta-subunit of F1-ATPase of Escherichia coli. Arch Biochem Biophys. 1988 Feb 15; 261(1):222-5.
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  123. Senior AE. ATP synthesis by oxidative phosphorylation. Physiol Rev. 1988 Jan; 68(1):177-231.
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  124. Rao R, Senior AE. The properties of hybrid F1-ATPase enzymes suggest that a cyclical catalytic mechanism involving three catalytic sites occurs. J Biol Chem. 1987 Dec 25; 262(36):17450-4.
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  125. Maggio MB, Pagan J, Parsonage D, Hatch L, Senior AE. The defective proton-ATPase of uncA mutants of Escherichia coli. Identification by DNA sequencing of residues in the alpha-subunit which are essential for catalysis or normal assembly. J Biol Chem. 1987 Jul 5; 262(19):8981-4.
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  126. Parsonage D, Wilke-Mounts S, Senior AE. Directed mutagenesis of the beta-subunit of F1-ATPase from Escherichia coli. J Biol Chem. 1987 Jun 15; 262(17):8022-6.
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  127. Rao R, Perlin DS, Senior AE. The defective proton-ATPase of uncA mutants of Escherichia coli: ATP-binding and ATP-induced conformational change in mutant alpha-subunits. Arch Biochem Biophys. 1987 Jun; 255(2):309-15.
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  128. Parsonage D, Duncan TM, Wilke-Mounts S, Kironde FA, Hatch L, Senior AE. The defective proton-ATPase of uncD mutants of Escherichia coli. Identification by DNA sequencing of residues in the beta-subunit which are essential for catalysis or normal assembly. J Biol Chem. 1987 May 5; 262(13):6301-7.
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  129. Wood JM, Wise JG, Senior AE, Futai M, Boyer PD. Catalytic properties of the F1-adenosine triphosphatase from Escherichia coli K-12 and its genetic variants as revealed by 18O exchanges. J Biol Chem. 1987 Feb 15; 262(5):2180-6.
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  130. Cox GB, Hatch L, Webb D, Fimmel AL, Lin ZH, Senior AE, Gibson F. Amino acid substitutions in the epsilon-subunit of the F1F0-ATPase of Escherichia coli. Biochim Biophys Acta. 1987 Feb 11; 890(2):195-204.
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  131. Duncan TM, Parsonage D, Senior AE. Structure of the nucleotide-binding domain in the beta-subunit of Escherichia coli F1-ATPase. FEBS Lett. 1986 Nov 10; 208(1):1-6.
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  132. Wise JG, Senior AE. Catalytic properties of the Escherichia coli proton adenosinetriphosphatase: evidence that nucleotide bound at noncatalytic sites is not involved in regulation of oxidative phosphorylation. Biochemistry. 1985 Nov 19; 24(24):6949-54.
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  133. Smith RA, Latchney LR, Senior AE. Tight divalent metal binding to Escherichia coli F1-adenosinetriphosphatase. Complete substitution of intrinsic magnesium by manganese or cobalt and studies of metal binding sites. Biochemistry. 1985 Jul 30; 24(16):4490-4.
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  134. Perlin DS, Latchney LR, Senior AE. Inhibition of Escherichia coli H+-ATPase by venturicidin, oligomycin and ossamycin. Biochim Biophys Acta. 1985 May 31; 807(3):238-44.
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  135. Duncan TM, Senior AE. The defective proton-ATPase of uncD mutants of Escherichia coli. Two mutations which affect the catalytic mechanism. J Biol Chem. 1985 Apr 25; 260(8):4901-7.
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  136. Perlin DS, Senior AE. Functional effects and cross-reactivity of antibody to purified subunit b (uncF protein) of Escherichia coli proton-ATPase. Arch Biochem Biophys. 1985 Feb 1; 236(2):603-11.
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  137. Perlin DS, Latchney LR, Wise JG, Senior AE. Specificity of the proton adenosinetriphosphatase of Escherichia coli for adenine, guanine, and inosine nucleotides in catalysis and binding. Biochemistry. 1984 Oct 9; 23(21):4998-5003.
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  138. Senior AE. Disposition of polar and nonpolar residues on outer surfaces of transmembrane helical segments of proteins involved in proton translocation. Arch Biochem Biophys. 1984 Oct; 234(1):138-43.
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  139. Wise JG, Latchney LR, Ferguson AM, Senior AE. Defective proton ATPase of uncA mutants of Escherichia coli. 5'-Adenylyl imidodiphosphate binding and ATP hydrolysis. Biochemistry. 1984 Mar 27; 23(7):1426-32.
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  140. Senior AE, Latchney LR, Ferguson AM, Wise JG. Purification of F1-ATPase with impaired catalytic activity from partial revertants of Escherichia coli uncA mutant strains. Arch Biochem Biophys. 1984 Jan; 228(1):49-53.
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  141. Wise JG, Duncan TM, Latchney LR, Cox DN, Senior AE. Properties of F1-ATPase from the uncD412 mutant of Escherichia coli. Biochem J. 1983 Nov 1; 215(2):343-50.
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  142. Cox GB, Jans DA, Gibson F, Langman L, Senior AE, Fimmel AL. Oxidative phosphorylation by mutant Escherichia coli membranes with impaired proton permeability. Biochem J. 1983 Oct 15; 216(1):143-50.
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  143. Perlin DS, Cox DN, Senior AE. Integration of F1 and the membrane sector of the proton-ATPase of Escherichia coli. Role of subunit "b" (uncF protein). J Biol Chem. 1983 Aug 25; 258(16):9793-800.
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  144. Fimmel AL, Jans DA, Langman L, James LB, Ash GR, Downie JA, Senior AE, Gibson F, Cox GB. The F1F0-ATPase of Escherichia coli. Substitution of proline by leucine at position 64 in the c-subunit causes loss of oxidative phosphorylation. Biochem J. 1983 Aug 1; 213(2):451-8.
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  145. Hamlyn JM, Senior AE. Evidence that Mg2+- or Ca2+-activated adenosine triphosphatase in rat pancreas is a plasma-membrane ecto-enzyme. Biochem J. 1983 Jul 15; 214(1):59-68.
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  146. Senior AE. Secondary and tertiary structure of membrane proteins involved in proton translocation. Biochim Biophys Acta. 1983 Jul 15; 726(2):81-95.
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  147. Jans DA, Fimmel AL, Langman L, James LB, Downie JA, Senior AE, Ash GR, Gibson F, Cox GB. Mutations in the uncE gene affecting assembly of the c-subunit of the adenosine triphosphatase of Escherichia coli. Biochem J. 1983 Jun 1; 211(3):717-26.
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  148. Senior AE, Langman L, Cox GB, Gibson F. Oxidative phosphorylation in Escherichia coli. Characterization of mutant strains in which F1-ATPase contains abnormal beta-subunits. Biochem J. 1983 Feb 15; 210(2):395-403.
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  149. Senior AE, Wise JG. The proton-ATPase of bacteria and mitochondria. J Membr Biol. 1983; 73(2):105-24.
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  150. Skerrett KJ, Wise JG, Latchney LR, Senior AE. Trypsin cleavage of the alpha-subunit of beef heart F1-ATPase abolishes ATP synthesis and ATP-driven energy-transduction capabilities. Biochim Biophys Acta. 1981 Nov 12; 638(1):120-4.
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  151. Wise JG, Latchney LR, Senior AE. The defective proton-ATPase of uncA mutants of Escherichia coli. Studies of nucleotide binding sites, bound aurovertin fluorescence, and labeling of essential residues of the purified F1-ATPase. J Biol Chem. 1981 Oct 25; 256(20):10383-9.
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  152. Cox GB, Downie JA, Langman L, Senior AE, Ash G, Fayle DR, Gibson F. Assembly of the adenosine triphosphatase complex in Escherichia coli: assembly of F0 is dependent on the formation of specific F1 subunits. J Bacteriol. 1981 Oct; 148(1):30-42.
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  153. Senior AE. Divalent metals in beef heart mitochondrial adenosine triphosphatase. Demonstration of the metals in membrane-bound enzyme and studies of the interconversion of the "1-Mg" and "2-Mg" forms of the enzyme. J Biol Chem. 1981 May 25; 256(10):4763-7.
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  154. Martin SS, Senior AE. Membrane adenosine triphosphatase activities in rat pancreas. Biochim Biophys Acta. 1980 Nov 4; 602(2):401-18.
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  155. Senior AE, Richardson LV, Baker K, Wise JG. Tight divalent cation-binding sites of soluble adenosine triphosphatase (F1) from beef heart mitochondria and Escherichia coli. J Biol Chem. 1980 Aug 10; 255(15):7211-7.
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  156. Senior AE. Tightly bound magnesium in mitochondrial adenosine triphosphatase from beef heart. J Biol Chem. 1979 Nov 25; 254(22):11319-22.
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  157. Senior AE, Fayle DR, Downie JA, Gibson F, Cox GB. Properties of membranes from mutant strains of Escherichia coli in which the beta-subunit of the adenosine triphosphatase is abnormal. Biochem J. 1979 Apr 15; 180(1):111-8.
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  158. Senior AE, Downie JA, Cox GB, Gibson F, Langman L, Fayle DR. The uncA gene codes for the alpha-subunit of the adenosine triphosphatase of Escherichia coli. Electrophoretic analysis of uncA mutant strains. Biochem J. 1979 Apr 15; 180(1):103-9.
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  159. Downie JA, Senior AE, Cox GB, Gibson F. Solubilization of adenosine triphosphatase from membranes of Escherichia coli: effect of p-aminobenzamidine. J Bacteriol. 1979 Apr; 138(1):87-91.
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  160. Downie JA, Senior AE, Gibson F, Cox GB. A fifth gene (uncE) in the operon concerned with oxidative phosphorylation in Escherichia coli. J Bacteriol. 1979 Feb; 137(2):711-8.
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  161. Smith RD, Hilf R, Senior AE. Prolactin binding to dissociated cells from rat mammary tumors and mammary gland. Cancer Biochem Biophys. 1979; 3(3):117-21.
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  162. Senior AE. Oligomycin-sensitivity-conferring protein. Methods Enzymol. 1979; 55:391-7.
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  163. Smith RD, Hilf R, Senior AE. The effect of altered thyroid state on prolactin binding to liver and 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats. Proc Soc Exp Biol Med. 1978 Sep; 158(4):517-20.
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  164. Leimgruber RM, Senior AE. Tightly-bound ATP and ADP in reconstituted submitochondrial particles. Biochem Biophys Res Commun. 1978 Aug 14; 83(3):837-42.
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  165. Smith RD, Hilf R, Senior AE. Prolactin binding to 7,12-dimethylbenz(a)anthracene-induced mammary tumors and liver in diabetic rats. Cancer Res. 1977 Nov; 37(11):4070-4.
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  166. Smith RD, Hilf R, Senior AE. Prolactin binding to R3230AC mammary carcinoma and liver in hormone-treated and diabetic rats. Cancer Res. 1977 Feb; 37(2):595-8.
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  167. Leimgruber RM, Senior AE. Removal of "tightly bound" nucleotides from soluble mitochondrial adenosine triphosphatase (F1). J Biol Chem. 1976 Nov 25; 251(22):7103-9.
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  168. Leimgruber RM, Senior AE. Removal of "tightly bound" nucleotides from phosphorylating submitochondrial particles. J Biol Chem. 1976 Nov 25; 251(22):7110-3.
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  169. Marinetti GV, Senior AE, Love R, Broadhurst CI. Reaction of amino-phospholipids of the inner mitochondrial membrane with fluorodinitrobenzene and trinitrobenzenesulfonate. Chem Phys Lipids. 1976 Oct; 17(2-3 SPEC NO):353-62.
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  170. Smith RD, Hilf R, Senior AE. Prolactin binding to mammary gland, 7,12-dimethylbenz(a)-anthracene-induced mammary tumors, and liver in rats. Cancer Res. 1976 Oct; 36(10):3726-31.
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  171. Senior AE, McGowan SE, Hilf R. A comparative study of inner membrane enzymes and transport systems in mitochondria from R3230AC mammary tumor and normal rat mammary gland. Cancer Res. 1975 Aug; 35(8):2061-7.
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  172. Senior AE. Mitochondrial adenosine triphosphatase. Location of sulfhydryl groups and disulfide bonds in soluble enzyme from beef heart. Biochemistry. 1975 Feb 25; 14(4):660-4.
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  173. Senior AE. The structure of mitochondrial ATPase. Biochim Biophys Acta. 1973 Dec 31; 301(3):249-77.
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  174. Senior AE. Relationship of cysteine and tyrosine residues to adenosine triphosphate hydrolysis by mitochondrial adenine triphosphatase. Biochemistry. 1973 Sep 11; 12(19):3622-7.
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  175. Holland PC, Senior AE, Sherratt HS. Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycaemic fatty acids. Effects of their coenzyme A esters on enzymes of fatty acid oxidation. Biochem J. 1973 Sep; 136(1):173-84.
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  176. Brooks JC, Senior AE. Methods for purification of each subunit of the mitochondrial oligomycin-insensitive adenosine triphosphatase. Biochemistry. 1972 Dec 5; 11(25):4675-8.
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  177. Wakabayashi T, Senior AE, Hatase O, Hayashi H, Green DE. Conformational changes in membranous preparations of cytochrome oxidase. J Bioenerg. 1972 Aug; 3(5):339-44.
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  178. Vanderkooi G, Senior AE, Capaldi RA, Hayashi H. Biological membrane structure. 3. The lattice structure of membranous cytochrome oxidase. Biochim Biophys Acta. 1972 Jul 3; 274(1):38-48.
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  179. Holland PC, Senior AE, Sherratt HS. Mechanism of inhibition of fatty acid oxidation by pent-4-enoic acid: 3-oxoacyl-coenzyme A thiolase as the possible site of inhibition. Biochem J. 1972 Apr; 127(3):79P-80P.
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  180. Brooks JC, Senior AE. Studies on the mitochondrial oligomycin-insensitive ATPase. II. The relationship of the specific protein inhibitor to the ATPase. Arch Biochem Biophys. 1971 Dec; 147(2):467-70.
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  181. Senior AE. On the relationship between the oligomycin-sensitivity conferring protein and other mitochondrial coupling factors. J Bioenerg. 1971 Aug; 2(3):141-50.
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  182. Blondin GA, DeCastro AF, Senior AE. The isolation and properties of a peptide ionophore from beef heart mitochondria. Biochem Biophys Res Commun. 1971 Apr 2; 43(1):28-35.
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  183. Senior AE, MacLennan DH. Mitochondrial "structural protein." A reassessment. J Biol Chem. 1970 Oct 10; 245(19):5086-95.
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  184. Senior AE, Brooks JC. Studies on the mitochondrial oligomycin-insensitivt ATPase. I. An improved method of purification and the behavior of the enzyme in solutions of various depolymerizing agents. Arch Biochem Biophys. 1970 Sep; 140(1):257-66.
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  185. Senior AE, Sherratt HS. A comparison of the effects on blood glucose and ketone-body levels, and of the toxicities, of pent-4-enoic acid and four simple fatty acids. J Pharm Pharmacol. 1969 Feb; 21(2):85-92.
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  186. Senior AE, Sherratt HS. Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycaemic fatty acids. Oxidative phosphorylation and mitochondrial oxidation of pyruvate, 3-hydroxybutyrate and tricarboxylic acid-cycle intermediates. Biochem J. 1968 Dec; 110(3):499-509.
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  187. Senior AE, Robson B, Sherratt HS. Biochemical effects of the hypoglycaemic compound pent--4-enoic acid and related non-hypoglycaemic fatty acids. Biochem J. 1968 Dec; 110(3):511-9.
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  188. Senior AE, Sherratt HS. Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycaemic fatty acids. Carbohydrate metabolism. Biochem J. 1968 Dec; 110(3):521-7.
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  189. Senior AE, Sherratt HS. The effect of pent-4-enoic acid and some simple related compounds on the oxidation of fatty acids by rat-liver mitochondria. Biochem J. 1967 Sep; 104(3):56P.
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