Quantum mechanical calculations of nucleophilic attack in the pseudouridine synthesis reaction

Ab initio quantum mechanical calculations at the MP2, level were performed to model nucleophilic attack in the pseudouridine synthesis reaction. The energy profile along the reaction coordinate suggests that the C1' attack by Asp may be the first step of the reaction, despite the fact that a COO- is a relatively weak nucleophile. This result supports the new mechanism proposed by Huang et al. for this enzyme.(1) Our calculations also showed that nucleophilic attack by Asp on C1' was stabilized by the uracil ring and that a similar stabilizing effect could exist in other nucleotides.