Research Topics
Species | Ian D KerrSummaryAffiliation: Imperial Cancer Research Fund Country: UK Publications
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Detail Information
Publications
Structure and association of ATP-binding cassette transporter nucleotide-binding domainsIan D Kerr
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Level 4, John Radcliffe Hospital, OX3 9DS, UK
Biochim Biophys Acta 1561:47-64. 2002..This review evaluates both these data and the conflicting implications they have for domain communication in ABC transporters. Areas of biochemical research that attempt to resolve these conflicts will be discussed...
Transmembrane helix 12 modulates progression of the ATP catalytic cycle in ABCB1Emily Crowley
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom
Biochemistry 48:6249-58. 2009..Overall, the results indicate that TM12 plays a key role in the progression of the ATP hydrolytic cycle in ABCB1, even in the absence of the transported substrate...
The coupling mechanism of P-glycoprotein involves residue L339 in the sixth membrane spanning segmentAlice Rothnie
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK
FEBS Lett 579:3984-90. 2005..However, covalent modification of this residue appears to prevent conformational changes that lead to drug stimulation of ATP hydrolysis...
Cytosolic region of TM6 in P-glycoprotein: topographical analysis and functional perturbation by site directed labelingJanet Storm
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, United Kingdom
Biochemistry 47:3615-24. 2008..Covalent modification of the cytosolic segment of TM6 did, however, attenuate drug stimulation of ATP hydrolysis and demonstrates an important role for this segment in coupling drug binding to ATP hydrolysis during translocation...
Residue G346 in transmembrane segment six is involved in inter-domain communication in P-glycoproteinJanet Storm
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom
Biochemistry 46:9899-910. 2007..Homology modeling of P-glycoprotein indicated that the G346C mutation caused a steric interaction between TM5 and TM6, thereby precluding a helical movement required to support ATP hydrolysis...
Purification and 3D structural analysis of oligomeric human multidrug transporter ABCG2Christopher A McDevitt
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, United Kingdom
Structure 14:1623-32. 2006..We interpret the tetrameric structure as comprising four homodimeric ABCG2(R482G) complexes...
Transmembrane helix 12 plays a pivotal role in coupling energy provision and drug binding in ABCB1Emily Crowley
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
FEBS J 277:3974-85. 2010..Taken together, these results indicate that TM12 plays a key role in the progression of the ATP hydrolytic cycle in ABCB1 and, in particular, in coordinating conformational changes between the NBDs and transmembrane domains...
The topography of transmembrane segment six is altered during the catalytic cycle of P-glycoproteinAlice Rothnie
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
J Biol Chem 279:34913-21. 2004..Our data are reconciled with a recent atomic scale model of P-gp and are consistent with a tilting of TM6 in response to nucleotide binding and ATP hydrolysis...
Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2?Christopher A McDevitt
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, UK
FEBS J 275:4354-62. 2008..The data indicate that, like ABCB1 and ABCC1, the 'power stroke' for translocation in ABCG2 R482G is the binding of nucleotide...
The translocation mechanism of P-glycoproteinRichard Callaghan
Nuffield Department of Clinical Laboratory Sciences, Level 4, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, United Kingdom
FEBS Lett 580:1056-63. 2006..The present review attempts to utilise the available data to generate a detailed sequence of events in the translocation pathway for this dexterous protein...
Purification and structural analyses of ABCG2Christopher A McDevitt
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, United Kingdom
Adv Drug Deliv Rev 61:57-65. 2009..ABCG2 is a structurally distinct member of the triumvirate of human multidrug transporters and continues to evade description of a unifying molecular mechanism...
Communication between the nucleotide binding domains of P-glycoprotein occurs via conformational changes that involve residue 508Mark P Gabriel
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, UK
Biochemistry 42:7780-9. 2003..The results imply that the accessibility of residue 508, located in the alpha-helical subdomain of NBD1 in Pgp, is altered by the conformational changes that occur during ATP hydrolysis...
The nucleotide-binding domains of P-glycoprotein. Functional symmetry in the isolated domain demonstrated by N-ethylmaleimide labellingGeorgina Berridge
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
Eur J Biochem 270:1483-92. 2003..Any observed functional asymmetry in the intact transporter presumably reflects different rates of hydrolysis at the two NBDs or interdomain communications...
P-glycoprotein: so many ways to turn it onRichard Callaghan
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
J Clin Pharmacol 48:365-78. 2008..This review also describes the mechanism underlying ABCB1 expression in noncancerous tissue, a process that does not involve the stress response...
An atomic detail model for the human ATP binding cassette transporter P-glycoprotein derived from disulfide cross-linking and homology modelingDaniella R Stenham
MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital Campus, London, UK
FASEB J 17:2287-9. 2003..This model will be important for understanding the mechanism of P-glycoprotein and other ABC transporters...
Sequence analysis of twin ATP binding cassette proteins involved in translational control, antibiotic resistance, and ribonuclease L inhibitionIan D Kerr
Centre for Biochemistry and Cell Biology, School of Biomedical Sciences, University of Nottingham, Queen s Medical Centre, Nottingham NG7 2UH, UK
Biochem Biophys Res Commun 315:166-73. 2004....
Nucleotide-dependent conformational changes in HisP: molecular dynamics simulations of an ABC transporter nucleotide-binding domainJeff D Campbell
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom
Biophys J 87:3703-15. 2004..These results support the mechanism for ATP-induced conformational transitions derived from the crystal structures of other NBDs...
Definition of the domain boundaries is critical to the expression of the nucleotide-binding domains of P-glycoproteinIan D Kerr
School of Biomedical Sciences, University of Nottingham, Queen s Medical Centre, Nottingham, NG7 2UH, UK
Eur Biophys J 32:644-54. 2003..We have interpreted our results in terms of homology models, which suggest that the N-terminal NBD of P-glycoprotein can be produced as a stable, correctly folded, isolate domain with judicious design of the expression construct...
Modelling the restoration of wild-type dynamic behaviour in DeltaF508-CFTR NBD1 by 8-cyclopentyl-1,3-dipropylxanthineDaniel J Warner
Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK
J Mol Graph Model 26:691-9. 2007....
