Searching for the minimum energy path in the sulfuryl transfer reaction catalyzed by human estrogen sulfotransferase: Role of enzyme dynamics

The enzymatic transfer of a sulfuryl group from the ubiquitous biological source of sulfate 3′‐phosphoadenosine 5′‐phosphosulfate (PAPS) to estrogen is investigated by the pseudo‐bond quantum mechanical/molecular mechanical method (QM/MM) method. Calculations of the reaction path are performed starting with models based on two crystal structures, which differ in information about the cofactor and substrates. In addition, a subsequent relaxation of the enzyme was performed with the found transition state frozen, followed by redetermination of the path. An activation barrier of 22 kcal/mol is estimated. The reaction mechanism features a proton transfer from the estrogen to a catalytic histidine followed by the rate determining SO 3 transfer. The mechanism found is largely dissociative. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006