The biological process of enzymatic sulfuryl group transfer has been studied by ab initio (density-functional and Hartree-Fock) and semiempirical quantum mechanical methods. The active site of estrogen sulfotransferase in ternary complex with a sulfate donor (PAPS) and sulfate acceptor (estradiol) is modeled. The mechanism proposed in a recent X-ray crystal structure paper (Kakuta et al., Nat. Struct. Biol. 4 (1997) 904) serves as the basis for the calculations. We find that the mechanism proposed in the crystallographic paper is reasonable. The sulfonation takes place in several key steps: neutralization of the charge on PAPS, lengthening of the bridging S-O bond with no cost in energy, activation of the attacking oxygen and proton transfer from estradiol to histidine and then to the sulfuryl group.
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