Modeling the reaction mechanisms for redox regulation of protein tyrosine phosphatase 1B activity |
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Authors: | Ning Liu Russell J Boyd |
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Institution: | (1) Department of Chemistry, Dalhousie University, Halifax, NS, Canada, B3H 4J3 |
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Abstract: | Protein tyrosine phosphatase 1B (PTP1B) functions by removing the phosphoryl group from tyrosinephosphorylated proteins in
insulin signaling and metabolism. The regeneration of the active site involves a sulphenylamide intermediate derived from
the intrastrand cross-linking between the catalytic serine and the neighboring backbone nitrogen. Two mechanisms have been
proposed for the formation of the sulphenylamide intermediate and the subsequent reactivation of the catalytic site. In the
current work, the proposed mechanisms have been investigated by the use of density functional theory calculations. Our results
suggest that these two mechanisms have similar overall energy barriers and that the preferred route will be determined by
the availability of hydrogen peroxide or other oxidizing reagents. |
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Keywords: | |
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