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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. May 2006, Volume 5, Number 5, 247-259 |
Quantitative in silico Analysis of Molecular Recognition and Reactivity
of D-Amino Acid Oxidase
Toshihiko Hanai
Internet Electron. J. Mol. Des. 2006, 5, 247-259
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Abstract:
Computational chemical analysis of enantiomer recognition with
chromatography was investigated using molecular mechanics
calculations. The method was applied to study enantiomer
recognition of the protein D-amino acid oxidase (DAAO). The
data for several stereo structures were obtained from databases,
and then the substrate was replaced with an amino acid, and the
new complexes were optimized using a MM2 calculation to
study the conformation of the amino acid complex. Mutant and
estimated human DAAO were constructed from the sequence
data and the known stereo structure of DAAO. The structures of
the new complexes with substituted amino acids were also
optimized using MM2 calculations, and used to study selectivity.
The reactivity was analyzed based on the atomic distances
calculated with MM2, and partial atomic charges calculated with
the MOPAC PM5 method. The values of atomic distances and
partial atomic charges indicate that the cationic hydrogen of the
amino acid could be moved to bind with the anionic nitrogen of
flavin. The selectivity of DAAO depends on the initial stereo
structure measured by X-ray crystallography and on the amino
acid included in the oxidation reaction site. Yeast DAAO has a
wider open entrance compared to pig kidney DAAO. The
selectivity of the co-enzyme was also analyzed using a
computational chemical calculation. The phosphate of flavin
mononucleotide (FMN) was caught by a guanidino group of the
enzyme, but that of flavin adenine dinucleotide (FAD) was free
from ion-ion interaction.
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