| Title
| - Electronic Structure, Ionization Potential, and Electron Affinity of the Enzyme Cofactor(6R)-5,6,7,8-Tetrahydrobiopterin in the Gas Phase, Solution, and Protein Environments
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| Abstract
| - (6R)-5,6,7,8-Tetrahydrobiopterin (BH4) is a key cofactor involved in the electron transfer to the P450 heme ofnitric oxide synthase. We calculated the electronic structure of the neutral, cationic, and anionic forms ofBH4 in the gas phase, in solution (both dielectric and explicit water), and in the protein environment usingdensity functional theory (B3LYP/6-31+G(d,p)). Subsequently, we derived the ionization potential (IP) andelectron affinity (EA) of the cofactor in these chemical environments. We found that the electronic structureof BH4 is susceptible to the presence of an external electric field and that conformational changes in thestructure of BH4 alone do not affect its electronic structure significantly. In the gas phase, water, and proteinenvironments neutral BH4 is the most stable species, while in the dielectric environment the anion becomesthe most stable species. The IP of BH4 in the protein environment is about half of that in the gas phase, andits EA is about 5 times smaller than that in the gas phase. Our results indicate that changes in the externalelectric field created by moving charged amino acid residues around BH4 may lead to configurations thathave the BH4 ion as stable as or more stable than the neutral form, thus facilitating the electron transfer.
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