Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 365231
Title Interaction of the indole class of vacuolar H+-ATPase inhibitors with lipid bilayers
Author(s) Fernandes, F.; Loura, L.; Koehorst, R.B.M.; Dixon, N.; Kee, T.P.; Hemminga, M.A.; Prieto, M.
Source Biochemistry 45 (2006)16. - ISSN 0006-2960 - p. 5271 - 5279.
Department(s) Biophysics
Publication type Refereed Article in a scientific journal
Publication year 2006
Keyword(s) membrane penetration depth - v-atpase - bone-resorption - fluorescence polarization - selective inhibitor - linear dichroism - energy-transfer - bafilomycin - orientation - tryptophan
Abstract The selective inhibitor of osteoclastic V-ATPase (2Z,4E)-5-(5,6-dichloro-2-indolyi)-2-methoxy-N-(1,2,2,6,6-pentamethylpip eridin-4-yl)-2,4-pentadienamide (SB 242784), member of the indole class of V-ATPase inhibitors, is expected to target the membrane-bound domain of the enzyme. A structural study of the interaction of this inhibitor with the lipidic environment is an essential step in the understanding of the mechanism of inhibition. In this work, a comprehensive study of the relevant features of this interaction was performed. Inhibitor partition coefficients to lipid vesicles as well as its transverse location, orientation (order parameters), and dynamics while bound to bilayers were determined through photophysical techniques, taking advantage of the intrinsic fluorescence of the molecule. To better evaluate the functionally relevant features of SB 242784, a second inhibitor, INH-1, from the same class and having a reduced activity was also examined. It is shown that regarding membrane interaction their properties remain very similar for both molecules, suggesting that the differences in inhibition efficiencies are solely a consequence of the molecular recognition processes within the inhibition site in the V-ATPase.
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