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Issue 2, 2009
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Metal-histidine-glutamate as a regulator of enzymatic cycles: a case study of carbonic anhydrase

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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.

Graphical abstract: Metal-histidine-glutamate as a regulator of enzymatic cycles: a case study of carbonic anhydrase

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Publication details

The article was received on 30 Jul 2008, accepted on 24 Sep 2008 and first published on 05 Nov 2008


Article type: Paper
DOI: 10.1039/B812916A
Citation: Phys. Chem. Chem. Phys., 2009,11, 374-383
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    Metal-histidine-glutamate as a regulator of enzymatic cycles: a case study of carbonic anhydrase

    G. Frison and G. Ohanessian, Phys. Chem. Chem. Phys., 2009, 11, 374
    DOI: 10.1039/B812916A

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