| Autor: |
Das R; Department of Chemistry , University of Houston , Houston , Texas 77204 , United States., Vázquez-Montelongo EA; Department of Chemistry , University of North Texas , Denton , Texas 76201 , United States., Cisneros GA; Department of Chemistry , University of North Texas , Denton , Texas 76201 , United States., Wu JI; Department of Chemistry , University of Houston , Houston , Texas 77204 , United States. |
| Abstrakt: |
Enzymes like uracil DNA glycosylase (UDG) can achieve ground state destabilization, by polarizing substrates to mimic rare tautomers. On the basis of computed nucleus independent chemical shifts, NICS(1) zz , and harmonic oscillator model of electron delocalization (HOMED) analyses, of quantum mechanics (QM) and quantum mechanics/molecular mechanics (QM/MM) models of the UDG active site, uracil is strongly polarized when bound to UDG and resembles a tautomer >12 kcal/mol higher in energy. Natural resonance theory (NRT) analyses identified a dominant O2 imidate resonance form for residue bound 1-methyl-uracil. This "tautomeric strain" raises the energy of uracil, making uracilate a better than expected leaving group. Computed gas-phase S N 2 reactions of free and hydrogen bonded 1-methyl-uracil demonstrate the relationship between the degree of polarization in uracil and the leaving group ability of uracilate. |
