Effects of structure on alpha C-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, modeled by HC(O)NHCH(R)C(O)NH(2) (PH(res)), were determined at the B3LYP/6-31G//B3LYP/6-31G level, coupled with isodesmic reactions. The results for neutral side chains with phi, psi angles approximately 180 degrees, approximately 180 degrees in ascending order, to an expected accuracy of +/-10 kJ mol(-)(1), are Asn 326; cystine 330; Asp 332; Gln 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; Ile 351; Val 352; Glu 354; Thr 357; Pro-cis 358; Pro-trans 369. BDEs calculated at the ROMP2/6-31G//B3LYP/6-31G level exhibit the same trends but are approximately 7 kJ mol(-)(1) higher. All BDEs are smaller than those of typical secondary or tertiary C-H bonds due to the phenomenon of captodative stabilization. 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 alpha C-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 current literature on H-transfer processes in enzyme mechanisms and in oxidative damage to proteins. These observations are discussed in terms of the findings of the present study.
Department of Chemistry, University of Calgary, Alberta, Canada.
A
A
Rauk
D
D
Yu
J
J
Taylor
G V
GV
Shustov
D A
DA
Block
D A
DA
Armstrong
D000596:Amino Acids / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D004735:Energy Transfer; D004798:Enzymes / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000596:Amino Acids; D004798:Enzymes; D005609:Free Radicals; D010455:Peptides; D011506:Proteins; D002244:Carbon; D006859:Hydrogen