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Searching for the minimum energy path in the sulfuryl transfer reaction catalyzed by human estrogen sulfotransferase: Role of enzyme dynamics
Author(s) -
Lin Ping,
Yang Weitao,
Pedersen Lars C.,
Negishi Masa,
Pedersen Lee G.
Publication year - 2006
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.21123
Subject(s) - chemistry , catalysis , cofactor , enzyme , molecular dynamics , stereochemistry , estrogen , enzyme catalysis , relaxation (psychology) , computational chemistry , organic chemistry , psychology , social psychology , biology , genetics
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