Dynamic conformations of flavin adenine dinucleotide: Simulated molecular dynamics of the flavin cofactor related to the time-resolved fluorescence characteristics

van den Berg, P. A. W., Feenstra, K. A., Mark, A. E., Berendsen, H. J. C. and Visser, A. J. W. G. (2002) Dynamic conformations of flavin adenine dinucleotide: Simulated molecular dynamics of the flavin cofactor related to the time-resolved fluorescence characteristics. Journal of Physical Chemistry B, 106 34: 8858-8869. doi:10.1021/jp020356s


Author van den Berg, P. A. W.
Feenstra, K. A.
Mark, A. E.
Berendsen, H. J. C.
Visser, A. J. W. G.
Title Dynamic conformations of flavin adenine dinucleotide: Simulated molecular dynamics of the flavin cofactor related to the time-resolved fluorescence characteristics
Journal name Journal of Physical Chemistry B   Check publisher's open access policy
ISSN 1520-6106
Publication date 2002-01-01
Sub-type Article (original research)
DOI 10.1021/jp020356s
Volume 106
Issue 34
Start page 8858
End page 8869
Total pages 12
Place of publication Washington
Publisher Amer Chemical Soc
Language eng
Abstract Molecular dynamics (MD) simulations and polarized subnanosecond time-resolved flavin fluorescence spectroscopy have been used to study the conformational dynamics of the flavin adenine dinucleotide (FAD) cofactor in aqueous solution. FAD displays a highly heterogeneous fluorescence intensity decay, resulting in lifetime spectra with two major components: a dominant 7-ps contribution that is characteristic of ultrafast fluorescence quenching and a 2.7-ns contribution resulting from moderate quenching. MD simulations were performed in both the ground state and first excited state. The simulations showed transitions from "open" conformations to "closed" conformations in which the flavin and adenine ring systems stack coplanarly. Stacking generally occurred within the lifetime of the flavin excited state (4.7 ns in water), and yielded a simulated fluorescence lifetime on the order of the nanosecond lifetime that was observed experimentally. Hydrogen bonds in the ribityl-pyrophosphate-ribofuranosyl chain connecting both ring systems form highly stable cooperative networks and dominate the conformational transitions of the molecule. Fluorescence quenching in FAD is mainly determined by the coplanar stacking of the flavin and adenine ring systems, most likely through a mechanism of photoinduced electron transfer. Whereas in stacked conformations fluorescence is quenched nearly instantaneously, open fluorescent conformations can stack during the lifetime of the flavin excited state, resulting in immediate fluorescence quenching upon stacking.
Keyword Chemistry, Physical
Coli Thioredoxin Reductase
Escherichia-coli
Glutathione-reductase
Lipoamide Dehydrogenase
Angstrom Resolution
Protein Nanospace
Electron-transfer
Crystal-structure
Wild-type
Spectroscopy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 20 Sep 2007, 01:34:51 EST