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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ping, L; Yang, W; Pedersen, LC; Negishi, M; Pedersen, LG

Published Date

  • November 15, 2006

Published In

Volume / Issue

  • 106 / 14

Start / End Page

  • 2981 - 2998

Electronic International Standard Serial Number (EISSN)

  • 1097-461X

International Standard Serial Number (ISSN)

  • 0020-7608

Digital Object Identifier (DOI)

  • 10.1002/qua.21123

Citation Source

  • Scopus