Metal-histidine-glutamate as a regulator of enzymatic cycles: a case study of carbonic anhydrase.Report as inadecuate




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* Corresponding author 1 DCMR - Laboratoire des mécanismes réactionnels

Abstract : Histidine is a very common metal ligand in metalloenzymes. Besides being an efficient Lewis base, its electronic properties are essential to shape the metal ability to catalyze the reaction. Here we show that histidine-s properties can be tuned, in turn, by an easy proton transfer to a nearby glutamate. We study this situation in Human Carbonic Anhydrase II HCA II in which one of the three histidines bound to zinc His119 interacts also with a glutamate residue Glu117. Proton transfer from His119 to Glu117 has been hypothesized in the past, however realistic modeling is performed here for the first time. We show that the carboxylate group of Glu117 behaves only as a hydrogen bond acceptor in the hydroxy form of HCA II. On the other hand, our results suggest that Glu117 could exist either as a hydrogen bond acceptor or as a proton acceptor in the aqua form of HCA II, the two isomers having almost the same thermodynamic stability. We propose that this proton shift may be used by the enzyme to facilitate the final displacement of bicarbonate by water.

Keywords : ZINC-BINDING-SITE AB-INITIO CALCULATIONS HYDROGEN-BOND NETWORK ACTIVE-SITE SEMIEMPIRICAL METHODS CATALYTIC MECHANISM ELECTRONIC-PROPERTIES PROTON-TRANSFER PROTEINS Zinc





Author: Gilles Frison - Gilles Ohanessian -

Source: https://hal.archives-ouvertes.fr/



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