Picomolar inhibition of β-galactosidase (bovine liver) attributed to loop closure

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Article - Abstract Only

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Inhibition, β-Galactosidase, Amidine, Carbohydrate


In an effort to examine similarities in the active sites of glycosidases within the GH35 family, we performed a structure-activity-relationship study using our recently described library of galactonoamidines. The kinetic evaluation based on UV/Vis spectroscopy disclosed inhibition of β-galactosidase (bovine liver) in the picomolar concentration range indicating significantly higher inhibitor affinity than previously determined for β-galactosidase (A. oryzae). Possible alterations in the secondary protein structure or folding were excluded after further examination of the inhibitor binding using CD spectroscopy. Molecular dynamics studies suggested loop closing interactions as a rationale for the disparity of the active sites in the β-galactosidases under investigation.


Support of this research to F. W. by the National Institutes of Health(1R01GM120578) and to S. S. by the National Science Foundation (CHE-1305543) and the Arkansas Biosciences Institute is gratefully acknowledged. The facilities used in this study were supported by Grant Number P30 GM103450 from the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH). The molecular dynamics simulations were performed in the Arkansas High-Performance Computing Center, which is supported by the National Science Foundation (ACI0722625, ACI0959124, ACI0963249, and ACI0918970) and the Division of Science and Technology at the Arkansas Economic Development Commission.

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