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Mechanistic Explanation of the Weak Carbonic Anhydrase's Esterase Activity
Paolo Piazzetta1, Tiziana Marino2, Nino Russo3
1Dipartimento di Chimica e Tecnologie Chimiche (CTC), Università della Calabria, 87036 Arcavacata di Rende (CS), Italy. paolo.piazzetta@unical.it.
Abstract:
In order to elucidate the elementary mechanism of the promiscuous esterase activity of human carbonic anhydrase (h-CA), we present an accurate theoretical investigation on the hydrolysis of fully-acetylated d-glucose functionalized as sulfamate. This h-CA's inhibitor is of potential relevance in cancer therapy. The study has been performed within the framework of three-layer ONIOM (QM-high:QM'-medium:MM-low) hybrid approach. The computations revealed that the hydrolysis process is not energetically favored, in agreement with the observed weak carbonic anhydrase's esterase activity.
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