Ian Kerr

Contact

• workRoom D72 University of Nottingham Medical School
  Queen's Medical Centre
  Nottingham
  NG7 2UH
  UK
• work0115 82 30122
• fax0115 82 30103
• ian.kerr@nottingham.ac.uk
• http://www.nottingham.ac.uk/~mbzidk

Research Summary

My research interests are the mechanisms and structures of proteins involved in transmembrane flux.

In particular, the group works on ATP binding cassette (ABC) transporters which are involved in multidrug efflux from cancer cells, and which are involved inthe clinical drug resistance of many tumour types. We have strong collaborations with the group of Beth Coyle to understand the role played by ABC transporters in pediatric brain tumour drug drug resistance, and with the group of Richard Callaghan to understand the mechanism of human ABC proteins.

Other projects that are in progress concern the Plasmodium chloroquine transporter, PfCRT, which is implicated in the failure of anti-malarial therapy (MRC funded collaboration with Richard Callaghan), and the function and mechanisms of auxin transporters in plants (collaboration with Malcolm Bennett and Ranjan Swarup).

Selected Publications

• HAIDER AJ, BRIGGS D, SELF TJ, CHILVERS HL, HOLLIDAY ND and KERR ID, 2011. Dimerization Of Abcg2 Analysed By Bimolecular Fluorescence Complementation. Plos One. 6(10), e25818
• SWARUP, R, BENKOVÁ, E, SWARUP, K, CASIMIRO, I, PÉRET, B, YANG, Y, PARRY, G, NIELSEN, E, DE SMET, I, VANNESTE, S, LEVESQUE, M, CARRIER, D, JAMES, N, CALVO, V, LJUNG, K, KRAMER, E, ROBERTS, R, GRAHAM, N, MARILLONNET, S, PATEL, K, JONES, J, TAYLOR, C, SCHACHTMAN, D, MAY, S, SANDBERG, G, BENFEY, P, FRIML, J, KERR, I, BEECKMAN, T, LAPLAZE, L and BENNETT, M., 2008. The auxin influx carrier LAX3 promotes lateral root emergence. Nature Cell Biology. 10(8), 946-954
• CARRIER,, ABU BAKAR,, SWARUP,, CALLAGHAN,, NAPIER,, BENNETT, and KERR,, 2008. The binding of auxin to the Arabidopsis auxin influx transporter, AUX1. Plant Physiology. 148, 1-7
• DORRIAN JM, BRIGGS DA, RIDLEY ML, LAYFIELD R, KERR ID, 2011. Induction of a stress response in Lactococcus lactis is associated with a resistance to ribosomally active antibiotics. FEBS Journal. 278(21), 4015-24

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• DORRIAN JM, BRIGGS DA, RIDLEY ML, LAYFIELD R, KERR ID, 2011. Induction of a stress response in Lactococcus lactis is associated with a resistance to ribosomally active antibiotics. FEBS Journal. 278(21), 4015-24
• DE SMET, IVE, VOSS, UTE, LAU, STEFFEN, WILSON, MICHAEL, SHAO, NING, TIMME, RUTH, SWARUP, RANJAN, KERR, IAN, HODGMAN, CHARLIE, BOCK, RALPH, BENNETT, MALCOLM, JÜRGENS, GERD and BEECKMAN, TOM, 2011. Unraveling the evolution of auxin signaling. Plant Physiology. 155, 209-221
• HAIDER AJ, BRIGGS D, SELF TJ, CHILVERS HL, HOLLIDAY ND and KERR ID, 2011. Dimerization Of Abcg2 Analysed By Bimolecular Fluorescence Complementation. Plos One. 6(10), e25818
• KERR ID, HAIDER AJ and GELISSEN IC, 2011. The Abcg Family Of Membrane-Associated Transporters: You Don't Have To Be Big To Be Mighty. British Journal Of Pharmacology. 164(7), 1767-79
• HUSSEIN, DEEMA, PUNJARUK, WIYADA, STORER, LISA C D, SHAW, LUCY, OTTOMAN, RAMADAN, PEET, ANDREW, MILLER, SUZANNE, BANDOPADHYAY, GAGORI, HEATH, RACHEL, KUMARI, RAJENDRA, BOWMAN, KAREN J, BRAKER, PAUL and R, 2010. Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion. Neuro-oncology. 13(1), 70-83
• CROWLEY, EMILY, O'MARA, MEGAN L, KERR, IAN D and CALLAGHAN, RICHARD, 2010. Transmembrane helix 12 plays a pivotal role in coupling energy provision and drug binding in ABCB1. The FEBS journal. 277(19), 3974-85
• KERR, IAN D, JONES, PETER M and GEORGE, ANTHONY M, 2010. Multidrug efflux pumps: the structures of prokaryotic ATP-binding cassette transporter efflux pumps and implications for our understanding of eukaryotic P-glycoproteins and homologues. The FEBS journal. 277(3), 550-63
• CHUTHAPISITH, S, BEAN, B, COWLEY, G, EREMIN, JM, SAMPHAO, S, LAYFIELD, R, KERR, ID, WISEMAN, J, EL-SHEEMY, M, SREENIVASAN, T, EREMIN, O, 2009. Annexins in human breast cancer: Possible predictors of pathological response to neoadjuvant chemotherapy. European Journal of Cancer. 45(7), 1274-81
• CROWLEY, EMILY, O'MARA, MEGAN L, REYNOLDS, CATHERINE, TIELEMAN, D PETER, STORM, JANET, KERR, IAN D and CALLAGHAN, RICHARD, 2009. Transmembrane helix 12 modulates progression of the ATP catalytic cycle in ABCB1. Biochemistry. 48(26), 6249-58
• FORD, R.C, KAMIS, A, KERR, I.D and & CALLAGHAN, R., 2009. The ABC Transporters: Structural insights into drug transport. In: ECKER, G and CHIBA, P. &MANNHOLD, R., eds., Transporters as Drug Carriers: Structure, Function, Substrates Wiley. 3-49
• CARRIER, DAVID JOHN, ABU BAKAR, NORLIZA TENDOT, LAWLER, KAREN, DORRIAN, JAMES MATTHEW, HAIDER, AMEENA, BENNETT, MALCOLM JOHN and KERR, IAN DEREK, 2009. Heterologous Expression of a Membrane-Spanning Auxin Importer: Implications for Functional Analyses of Auxin Transporters. International journal of plant genomics. 2009, 848145
• DORRIAN J.M. & KERR, I.D., 2009. Can ABC proteins confer drug resistance in micro-organisms without being export pumps?. In: PONTE-SUCRE, A., ed., ABC Transporters in Microorganisms Horizon Press. 45-54
• MCDEVITT, CHRISTOPHER A, COLLINS, RICHARD, KERR, IAN D and CALLAGHAN, RICHARD, 2009. Purification and structural analyses of ABCG2. Advanced drug delivery reviews. 61(1), 57-65
• SWARUP, R, BENKOVÁ, E, SWARUP, K, CASIMIRO, I, PÉRET, B, YANG, Y, PARRY, G, NIELSEN, E, DE SMET, I, VANNESTE, S, LEVESQUE, M, CARRIER, D, JAMES, N, CALVO, V, LJUNG, K, KRAMER, E, ROBERTS, R, GRAHAM, N, MARILLONNET, S, PATEL, K, JONES, J, TAYLOR, C, SCHACHTMAN, D, MAY, S, SANDBERG, G, BENFEY, P, FRIML, J, KERR, I, BEECKMAN, T, LAPLAZE, L and BENNETT, M., 2008. The auxin influx carrier LAX3 promotes lateral root emergence. Nature Cell Biology. 10(8), 946-954
• CARRIER,, ABU BAKAR,, SWARUP,, CALLAGHAN,, NAPIER,, BENNETT, and KERR,, 2008. The binding of auxin to the Arabidopsis auxin influx transporter, AUX1. Plant Physiology. 148, 1-7
• STORM, JANET, MODOK, SZABOLCS, O'MARA, MEGAN L, TIELEMAN, D PETER, KERR, IAN D and CALLAGHAN, RICHARD, 2008. Cytosolic region of TM6 in P-glycoprotein: topographical analysis and functional perturbation by site directed labeling. Biochemistry. 47(12), 3615-24
• MCDEVITT,, CROWLEY,, HOBBS,, STARR,, KERR, and CALLAGHAN,, 2008. Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2? The FEBS Journal.
• LAWSON, J, O'MARA, M L and KERR, I D, 2008. Structure-based interpretation of the mutagenesis database for the nucleotide binding domains of P-glycoprotein. Biochimica et Biophysica Acta. 1778(2), 376-91
• CALLAGHAN, RICHARD, CROWLEY, EMILY, POTTER, SIMON and KERR, IAN D, 2008. P-glycoprotein: so many ways to turn it on. Journal of Clinical Pharmacology. 48(3), 365-78
• CHUTHAPISITH, S, LAYFIELD, R, KERR, I D and EREMIN, O, 2007. Principles of proteomics and its applications in cancer. The Surgeon. 5(1), 14-22
• CHUTHAPISITH, S, LAYFIELD, R, KERR, ID, HUGHES, C, EREMIN, O, 2007. Proteomic profiling of MCF-7 breast cancer cells with chemoresistance to different types of anti-cancer drugs. International Journal of Oncology. 30(6), 1545-51
• WARNER,, VADOLIA,, LAUGHTON,, KERR, and DOUGHTY,, 2007. Modelling the restoration of wild-type dynamic behaviour in DeltaF508-CFTR NBD1 by 8-cyclopentyl-1,3-dipropylxanthine. Journal of Molecular Graphics and Modelling. 26, 691-699
• KERR, IAN D and BENNETT, MALCOLM J, 2007. New insight into the biochemical mechanisms regulating auxin transport in plants. Biochemical Journal. 401(3), 613-22
• STORM,, O'MARA,, CROWLEY,, PEALL,, TIELEMAN,, KERR, and CALLAGHAN,, 2007. Residue G346 in Transmembrane Segment Six is Involved in Inter-Domain Communication in P-Glycoprotein. Biochemistry. 46(35), 9899-9910
• CLARK, R, KERR, I D and CALLAGHAN, R, 2006. Multiple drugbinding sites on the R482G isoform of the ABCG2 transporter. British Journal of Pharmacology. 149(5), 506-15
• KERR, I. D. and SIMPKINS, N. S., 2006. ABC Transporters and Isothiocyanates LETTERS IN DRUG DESIGN AND DISCOVERY. VOL 3(NUMB 9), 607-621
• MCDEVITT, CHRISTOPHER A, COLLINS, RICHARD F, CONWAY, MICHAEL, MODOK, SZABOLCS, STORM, JANET, KERR, IAN D, FORD, ROBERT C and CALLAGHAN, RICHARD, 2006. Purification and 3D structural analysis of oligomeric human multidrug transporter ABCG2. Structure. 14(11), 1623-32
• CALLAGHAN, RICHARD, FORD, ROBERT C and KERR, IAN D, 2006. The translocation mechanism of P-glycoprotein. FEBS Letters. 580(4), 1056-63
• ROTHNIE, A., STORM, J., MCMAHON, R., TAYLOR, A., KERR, I.D. and CALLAGHAN, R, 2005. The coupling mechanism of P-glycoprotein involves residue L339 in the sixth membrane spanning segment. FEBS Letters. 579(18), 3984-3990
• KERR, I D, REYNOLDS, E D and COVE, J H, 2005. ABC proteins and antibiotic drug resistance: is it all about transport? Biochemical Society Transactions. 33(Pt 5), 1000-2
• SWARUP, R., KARGUL, J., MARCHANT, A., ZADIK, D., RAHMAN, A., MILLS, R., YEMM, A., MAY, S., WILLIAMS, L., MILLNER, P., TSURUMI, S., MOORE, I., NAPIER, R., KERR, I.D. and BENNETT, M.J., 2004. Structure-function analysis of the presumptive Arabidopsis auxin permease AUX1 Plant Cell. 16(11), 3069-3083
• ROTHNIE, A., STORM, J., CAMPBELL, J., LINTON, K.J., KERR, I.D. and CALLAGHAN, R, 2004. The topography of transmembrane segment six is altered during the catalytic cycle of P-glycoprotein. Journal of Biological Chemistry. 279(33), 34913-34921
• KERR, I.D, 2004. Sequence analysis of twin ATP binding cassette proteins involved in translational control, antibiotic resistance, and ribonuclease L inhibition. Biochemical and Biophysical Research Communications. 315(1), 166-173
• CAMPBELL, JEFF D, DEOL, SUNDEEP SINGH, ASHCROFT, FRANCES M, KERR, IAN D and SANSOM, MARK S P, 2004. Nucleotide-dependent conformational changes in HisP: molecular dynamics simulations of an ABC transporter nucleotide-binding domain. Biophysical Journal. 87(6), 3703-15
• STENHAM, D.R., CAMPBELL, J.D., SANSOM, M.S.P., HIGGINS, C.F., KERR, I.D. and LINTON, K.J., 2003. An atomic detail model for the human ATP binding cassette transporter P-glycoprotein derived from disulfide cross-linking and homology modeling FASEB Journal. 17(15), 2287-2289
• BERRIDGE, G., WALKER, J. A., CALLAGHAN, R. and KERR, I. D., 2003. The nucleotide-binding domains of P-glycoprotein. Functional symmetry in the isolated domain demonstrated by N-ethylmaleimide labelling European Journal of Biochemistry. 270(7), 1483-1492
• KERR, IAN D, BERRIDGE, GEORGINA, LINTON, KENNETH J, HIGGINS, CHRISTOPHER F and CALLAGHAN, RICHARD, 2003. Definition of the domain boundaries is critical to the expression of the nucleotide-binding domains of P-glycoprotein. European Biophysics Journal. 32(7), 644-54
• GABRIEL, MARK P, STORM, JANET, ROTHNIE, ALICE, TAYLOR, ANDREW M, LINTON, KENNETH J, KERR, IAN D and CALLAGHAN, RICHARD, 2003. Communication between the nucleotide binding domains of P-glycoprotein occurs via conformational changes that involve residue 508. Biochemistry. 42(25), 7780-9
• KERR, IAN D, 2002. Structure and association of ATP-binding cassette transporter nucleotide-binding domains. Biochimica et Biophysica Acta. 1561(1), 47-64
• ROSENBERG, M. F., VELARDE, G., FORD, R. C., MARTIN, C., BERRIDGE, G., KERR, I. D., CALLAGHAN, R., SCHMIDLIN, A., WOODING, C. and LINTON, K. J., 2001. Repacking of the transmembrane domains of P-glycoprotein during the transport ATPase cycle EMBO Journal. VOL 20(PART 20), 5615-5625
• SON, H S, KERR, I D and SANSOM, M S, 2000. Simulation studies on bacteriorhodopsin bundle of transmembrane alpha segments. European Biophysics Journal. 28(8), 663-73
• RANATUNGA, K M, KERR, I D, ADCOCK, C A, SMITH, G R and SANSOM, M S, 1998. Molecular dynamics of ion/channel interactions. Biochemical Society Transactions. 26(3), S301
• SANSOM, M S, KERR, I D, LAW, R, DAVISON, L and TIELEMAN, D P, 1998. Modelling the packing of transmembrane helices: application to aquaporin-1. Biochemical Society Transactions. 26(3), 509-15
• RANATUNGA, K M, KERR, I D, ADCOCK, C, SMITH, G R and SANSOM, M S, 1998. Protein-water-ion interactions in a model of the pore domain of a potassium channel: a simulation study. Biochimica et Biophysica Acta. 1370(1), 1-7
• GRICE, A L, KERR, I D and SANSOM, M S, 1997. Ion channels formed by HIV-1 Vpu: a modelling and simulation study. FEBS Letters. 405(3), 299-304
• KERR, I D and SANSOM, M S, 1997. The pore-lining region of shaker voltage-gated potassium channels: comparison of beta-barrel and alpha-helix bundle models. Biophysical Journal. 73(2), 581-602
• SANSOM, M S, KERR, I D, SMITH, G R and SON, H S, 1997. The influenza A virus M2 channel: a molecular modeling and simulation study. Virology. 233(1), 163-73
• SCHMITT, J D, SANSOM, M S, KERR, I D, LUNT, G G and EISENTHAL, R, 1997. Ferrocenoyl derivatives of alamethicin: redox-sensitive ion channels. Biochemistry. 36(5), 1115-22
• BREED, J, BIGGIN, P C, KERR, I D, SMART, O S and SANSOM, M S, 1997. Alamethicin channels - modelling via restrained molecular dynamics simulations. Biochimica et Biophysica Acta. 1325(2), 235-49
• BREED, J, KERR, I D, MOLLE, G, DUCLOHIER, H and SANSOM, M S, 1997. Ion channel stability and hydrogen bonding. Molecular modelling of channels formed by synthetic alamethicin analogues. Biochimica et Biophysica Acta. 1330(2), 103-9