A quantum mechanical study of the transfer of biological sulfate

Abstract

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.