  1.4.1.B2 | metabolism |
in the proposed mechanism, the catalytic cycle starts with the hydride transfer from C3 of L-erythro-3,5-diaminohexanoate to C4 of NADP+ with a barrier of 18.8 kcal/mol. The generated iminium intermediate (Int1) is 1.8 kcal/mol lower than the ternary complex E:DAH. In the next hydration step, both the deprotonated C5-amino group of L-erythro-3,5-diaminohexanoate and D177 can be the catalytic base to activate the water molecule that attacks the electrophilic carbon of Int1. The barrier is 8.3 kcal/mol or 12.4 kcal/mol relative to Int1 for the pathways with C5-amino group or D177, respectively. For the former pathway, after the formation of hydrated intermediate (Int2), a proton transfer takes place from the protonated C5-amino group to D177 via the newly formed hydroxyl group with a barrier of 10.7 kcal/mol relative to Int1, arriving at the same intermediate (Int3) as the latter pathway. Then, a proton transfer from D177 to C3-amino group results in intermediate Int4 with -0.1 kcal/mol energy, in which the protonated amino group can be significantly stabilized by the carboxylate groups of D49 and D177. Finally, the products are formed by the C-N bond cleavage, concurrently with intramolecular proton transfer from the C3-hydroxyl group to the C5-amine |
-, 762604 |
