Effects of structure on C-alpha-H bond enthalpies of amino acid residues: Relevance to H transfers in enzyme mechanisms and in protein oxidation

The bond dissociation enthalpies (BDE) of all of the amino acid residues, m odeled by HC-(O)NHCH(R)C(O)NH2 (PH(res)), were determined at the B3LYP/6-31 G*//B3LYP/6-31G* level, coupled with isodesmic reactions. The results for n eutral side chains with phi,psi angles similar to 180 degrees,similar to 18 0 degrees in ascending order, to an expected accuracy of +/-10 kJ mol(-1), are Asn 326; cystine 330; Asp 332; Gin 334; Trp 337; Arg 340; Lys 340; Met 343; His 344; Phe 344; Tyr 344; Leu 344; Ala 345; Cys 346; Ser 349; Gly 350 ; ne 351; Val 352; Glu 354; Thr 357; Pro-cis 358; Pro-trans 369. BDEs calcu lated at the ROMP2/6-31G*// B3LYP/6-31G* level exhibit the same trends but are similar to 7 kJ mol(-1) higher. All BDEs are smaller than those of typi cal secondary or tertiary C-H bonds due to the phenomenon of captodative st abilization. The stabilization is reduced by changes in the phi,psi, angles . As a result the BDEs increase by about 10 kJ mol(-1) in beta-sheet and 40 kJ mol(-1) in alpha-helical environments, respectively. In effect the C-al pha-H BDEs can be "tuned" from about 345 to 400 kJ mol(-1) by adjusting the local environment. Some very significant effects of this are seen in the c urrent literature on H-transfer processes in enzyme mechanisms and in oxida tive damage to proteins. These observations are discussed in terms of the f indings of the present study.