Abstract
The interactions of Selenocysteine (Sec) with Ca have been investigated through the use of B3LYP/6-311+G(3df,2p)//B3LYP/6-311+G(d,p) calculations. The global minimum of the [SecCa] potential energy surface is a charge-solvated (CS) species in which the metal dication is bound to the SeH, to the amino groups and to the carbonyl oxygen. Within a gap of 5.0 kJ mol in terms of free energies there are four more complexes three of which are salt-bridged (SB) structures. The interactions between Ca and the amino acid are essentially electrostatic, in contrast with what happens when Ca is replaced by Cu, where the charge transfer from Sec to the metal cation is so large that in the [Sec-Cu] global minimum the amino acid moiety is oxidized. The significant electron density redistribution undergone by the amino acid when interacting with both doubly-charged metal ions is reflected in a significant enhancement of its intrinsic acidity, although this effect is much larger for Cu than for Ca. One of the direct consequences of the oxidation undergone by the amino acid when attached to Cu is that the complexes formed are thermodynamically unstable with respect to a proton loss since the process Sec + Cu → [(Sec-H)Cu] + H is strongly exothermic. Conversely, a similar process when Cu is replaced by Ca is endothermic and therefore the [Sec-Ca] complexes should be stable with respect to a proton loss.
Highlights
Selenocysteine (Sec) is considered the 21st amino acid and it is found in all kind of living beings as a building block of selenoproteins,[1] which have been found to be essential in mammals.[2]
The global minimum of the [Sec-Ca]2+ potential energy surface is a CS species in which the metal dication is bound to the three basic groups of the amino acid, namely the carbonyl oxygen, the SeH and the amino groups, but within a gap of 5.0 kJ mol-1 in terms of free energies there are other four complexes, three of which are SB structures
The interactions between Ca2+ and the amino acid are essentially electrostatic, in contrast with what happens when Ca2+ is replaced by Cu2+, where the charge transfer from Sec to the metal cation is so large that in the [Sec-Cu]2+ global minimum the amino acid moiety is oxidized
Summary
Selenocysteine (Sec) is considered the 21st amino acid and it is found in all kind of living beings as a building block of selenoproteins,[1] which have been found to be essential in mammals.[2] the first selenoprotein identified in mammals, namely glutathione peroxidase, protect cells from oxidative damage.[3] a great majority of selenoproteins are enzymes involved in redox reactions.[1,2, 4,5] This is, for instance the case of formate dehydrogenase which catalyzes the oxidation of formate to carbon dioxide, and in which the presence of Sec seems to play a crucial role in the mechanism of the reaction.[6] It seems well established that Sec-containing enzymes modulate and play some role in brain diseases, such as Parkinson's disease or epilepsy,[5, 7] and that the deficiency of some Sec-containing enzymes seems to be closely related with stroke risk,[8] whereas several others have been implicated in the risk or development of cancer.[9] importantly, 25 human genes encoding selenoproteins have been already identified,[10] little is known, for the time being, about their biological functions.[11]
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