A comparative study of the single crystal X-ray determination and molecular modelling of the binding of oligomycin to ATP Synthase
Green, R.C.E. and Thumser, A.E. and Povey, D. and Saldanha, J.W. and Potter, B.S. and Palmer, Rex A. and Howlin, B.J. (2009) A comparative study of the single crystal X-ray determination and molecular modelling of the binding of oligomycin to ATP Synthase. Computational Biology and Chemistry 33 (3), pp. 189-195. ISSN 1476-9271.
Abstract
Recently published X-ray structures of three common forms, A, B and C, of oligomycin, including absolute configurations, are investigated to examine their binding to ATP Synthase. The X-ray studies reveal regions with differences in three-dimensional structure and hydrogen bonding propensity between the oligomycins, which may be associated with their potential to bind to sites on ATP Synthase. Computational docking studies carried out using MOE with the X-ray structures and an homology model of the FO domain of ATP Synthase from Escherichia coli, are used to derive an induced fit pocket. Docking of all oligomycins to this pocket indicate that the B and C forms bind more tightly than the A form. Consideration of the single crystal X-ray data alone indicate the B form may be the best inhibitor and that O(24) is the most important ligating group for binding, this is supported by the docking data. The latter reveals Asn214 and other key proton translocating residues to be the main residues contacted by the inhibitor. These data allow the binding modes of different forms of oligomycin to be deduced from X-ray single crystal data supported by molecular modelling and computational docking studies.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | Oligomycin, antibiotic, ATP Synthase inhibitor, modelling the oligomycin binding site |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Administrator |
| Date Deposited: | 27 Jul 2011 14:37 |
| Last Modified: | 02 Aug 2023 16:55 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/3890 |
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