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Theoretical study on charge-transfer interaction between acyl-CoA dehydrogenase and 3-thiaacyl-CoA using density
Takeyuki Tanaka1, Haruhiko Tamaoki, Yasuzo Nishina
1Department of Biosystems Science, Graduate School of Science and Technology, Kobe University, 1-1 Rokodai-cho, Nada-ku, Kobe 657-8501. putaro@protein.osaka-u.ac.jp
Journal of Biochemistry
|June 6, 2006
Summary
This study optimized complex models of flavin adenine dinucleotide (FAD) and its analogs using density functional theory (DFT). The findings reveal electrostatic and hydrogen-bonding interactions are crucial for understanding charge-transfer (CT) complexes in enzymatic reactions.
Area of Science:
- Biochemistry
- Computational Chemistry
- Molecular Biophysics
Background:
- Acyl-CoA dehydrogenase forms charge-transfer (CT) complexes with substrate analogs.
- Understanding these CT complexes is vital for elucidating enzymatic mechanisms.
Purpose of the Study:
- To computationally model and analyze the structural and electronic properties of flavin-ligand complexes.
- To investigate the role of electrostatic and hydrogen-bonding interactions in CT complex formation.
- To correlate computational predictions with experimental observations of CT bands.
Main Methods:
- Density Functional Theory (DFT) calculations for full geometry optimization of complex models.
- Calculation of excitation energies and oscillator strengths for optimized structures.
- Systematic variation of substituents and hydrogen-bonding interactions in the models.
Main Results:
- Optimized structures of lumiflavin and FAD complex models showed good agreement with experimental X-ray data.
- Calculated excitation wavelengths correlated well with experimentally observed CT band values.
- Redesigned models incorporating hydrogen bonds demonstrated improved correlation with experimental data.
Conclusions:
- Electrostatic interactions significantly influence the arrangement of CT complexes.
- Hydrogen bonding, particularly at the FAD N10-ribityl 2'-hydroxyl and Glu376 amide, plays a critical role in stabilizing CT complexes.
- Computational analysis of substituent effects provides insights into CT interactions and their modulation by hydrogen bonding.