Model Study
Using Designed Selenopeptides on the Importance
of the Catalytic Triad for the Antioxidative Functions of Glutathione
Peroxidase
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Abstract
Although
the catalytic triad of glutathione peroxidase (GPx) has
been well recognized, there was little evidence for the relevance
of the interactions among the triad amino acid residues, i.e., selenocysteine
(U), glutamine (Q), and tryptophan (W), to the GPx antioxidative functions.
Using a designed selenopeptide having an amino acid sequence of GQAUAWG,
we demonstrate here that U, Q, and W present at the active site can
interact with each other to exert the enzymatic activity. The amino
acid sequence was chosen on the basis of the Monte Carlo molecular
simulation for various selenopeptides in polarizable continuous water
using the SAAP force field (SAAP-MC). Measurement of the GPx-like
activity for the selenopeptide obtained by solid-phase peptide synthesis
revealed that the antioxidant activity is cooperatively enhanced by
the presence of Q and W proximate to U, although the activity was
low compared to selenocystine (U<sub>2</sub>). The effect of Q on
the activity was more important than that of W. In addition, the fluorescence
spectrometry suggested a close contact between U and W. These experimental
observations were supported by SAAP-MC simulation as well as by ab
initio calculation. The latter further suggested that the interaction
mode among the triad changes depending on the intermediate states