Strength of the CαH··O Hydrogen Bond of Amino Acid Residues

Abstract

Although the peptide CαH group has historically not been thought to form hydrogen bonds within proteins, ab initio quantum calculations show it to be a potent proton donor. Its binding energy to a water molecule lies in the range between 1.9 and 2.5 kcal/mol for nonpolar and polar amino acids; the hydrogen bond (H-bond) involving the charged lysine residue is even stronger than a conventional OH··O interaction. The preferred H-bond lengths are quite uniform, about 3.32 Å. Formation of each interaction results in a downfield shift of the bridging hydrogen's chemical shift and a blue shift in the CαH stretching frequency, potential diagnostics of the presence of such an H-bond within a protein. Although the peptide CαH group has historically not been thought to form hydrogen bonds within proteins, ab initio quantum calculations show it to be a potent proton donor. Its binding energy to a water molecule lies in the range between 1.9 and 2.5 kcal/mol for nonpolar and polar amino acids; the hydrogen bond (H-bond) involving the charged lysine residue is even stronger than a conventional OH··O interaction. The preferred H-bond lengths are quite uniform, about 3.32 Å. Formation of each interaction results in a downfield shift of the bridging hydrogen's chemical shift and a blue shift in the CαH stretching frequency, potential diagnostics of the presence of such an H-bond within a protein. hydrogen bond and hydrogen bonding, respectively Whereas conventional hydrogen bonds that involve electronegative atoms like oxygen and nitrogen have been thoroughly studied over the decades since their first introduction into the literature and are presently well understood (1Jeffrey G.A. Saenger W. Hydrogen Bonding in Biological Structures. Springer-Verlag, Berlin1991Crossref Google Scholar, 2Smith, D. A. (ed) (1994) Am. Chem. Soc. Symp. 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The of the atoms the and results in the amino acid the groups are as the might only a upon the binding energy in the with In fact, of in that and have H-bond The of upon the of each of amino of hydrogen the residue and a of the interaction energy of the group of to the group of valine the binding energy It is to that the larger of and would be to the for and that the binding of of amino in the range between and 2.5 The residue the polar group in its its H-bond energy of kcal/mol within the range of the nonpolar In a of the the of hydrogen of the group the electronegative the H-bond energy some In the of the residue the binding energy of In the H-bond of the amino including polar and less polar are quite to in the kcal/mol to the charged first the lysine residue with its It is to the to the CαH group a proton its H-bond to as with conventional H-bonds. This is in the of the residue, with a binding energy of about that of the the group the is bonds from the of In fact, CH··O H-bond is stronger than the conventional OH··O of the water now to the of the potential for the interaction between the residue and a water It be first noted that a a of about Å. A of H-bond as as or an the groups the has or and the energy has to 2.5 kcal/mol the the from to to the groups even This range is the of the between the and the of the water In interaction a H-bond of about 2.5 since that is the energy to the in the be about the of the H-bond energy in such a case, since that the is in energy than the The is less in the of the amino acids where the have The of the between and the in is a in where the H-bond energy is as the energy of the to In to be an interaction that the of the residue from their range repulsive interaction. It is but that the of is in to the H-bond of the amino The of the between the proton and the oxygen of the water the preferred H-bond This is with with stronger H-bonds with a It is to that H-bond is in CH··O a range between and Å. This range quite well with the H-bond of neutron diffraction for the interaction between a CαH group and a water molecule T. J. Chem. Soc. 1995; Google Scholar), as well as the of in β-sheets (38Fabiola G.F. Krishnaswamy S. Nagarajan V. Pattabhi V. Acta Crystallogr. D. 1997; 53: 316-320Crossref PubMed Scopus (148) Google Scholar). The H-bond is about for as well as for the amino acids and It to for the and Despite the stronger binding of the residue, its H-bond of 3.32 is in the same range as the as is the for the The of the of the CH··O H-bond upon the CH bond is in the of The first the in the water a that is of conventional OH··O This with the that occur in the CH··O H-bonds of amino acids as well as This in a number of CH··O bonds P. V. J. Phys. Chem. 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T. S. J. Am. Chem. Soc. 1999; 121: Scopus Google the of a CH··O interaction is stretching or from its than are OH··O even if the is weaker than the are in their preferred the can with the or which are the than the in into the of the CH··O bond and its to bond interaction cannot be the various that to protein Indeed, the of such bonds be an important in the presence of water within the of The of the CαH··O interaction a genuine H-bond is not to the binding energy but involves of the as well. Y. T. S. J. Am. Chem. 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