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.
Rauk
A
A
Department of Chemistry, University of Calgary, Alberta, Canada.
Yu
D
D
Taylor
J
J
Shustov
G V
GV
Block
D A
DA
Armstrong
D A
DA
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