%0 Journal Article %1 hlwoodcock:Alhambra1998 %A Alhambra, C. %A Wu, L. %A Zhang, Z. Y. %A Gao, J. L. %D 1998 %J JOURNAL OF THE AMERICAN CHEMICAL SOCIETY %K bibtex-import %N 16 %P 3858--3866 %T Walden-inversion-enforced transition-state stabilization in a protein tyrosine phosphatase %V 120 %X The initial step of the dephosphorylation reaction of a tyrosine phosphate substrate catalyzed by the low molecular weight bovine protein tyrosine phosphatase (BPTP) has been studied, making use of a combined quantum mechanical and molecular mechanical approach in molecular dynamics simulations. It was found that the enzyme favors a dianion substrate in the dephosphorylation reaction, which is consistent with experiments but in contrast to a recent mechanistic proposal involving a monoanion phosphate. The computed activation free energy is ca. 14 kcal/mol, in accord with the activation parameters determined in the present study from stopped-flow kinetics experiments. Structural analyses support the finding that BPTP catalyzes dephosphorylation reactions by stabilizing the transition state through Walden-inversion-enforced hydrogen-bonding interactions during the S(N)2 process.

@article{hlwoodcock:Alhambra1998, abstract = {The initial step of the dephosphorylation reaction of a tyrosine phosphate substrate catalyzed by the low molecular weight bovine protein tyrosine phosphatase (BPTP) has been studied, making use of a combined quantum mechanical and molecular mechanical approach in molecular dynamics simulations. It was found that the enzyme favors a dianion substrate in the dephosphorylation reaction, which is consistent with experiments but in contrast to a recent mechanistic proposal involving a monoanion phosphate. The computed activation free energy is ca. 14 kcal/mol, in accord with the activation parameters determined in the present study from stopped-flow kinetics experiments. Structural analyses support the finding that BPTP catalyzes dephosphorylation reactions by stabilizing the transition state through Walden-inversion-enforced hydrogen-bonding interactions during the S(N)2 process.}, added-at = {2006-06-16T05:03:46.000+0200}, author = {Alhambra, C. and Wu, L. and Zhang, Z. Y. and Gao, J. L.}, biburl = {https://www.bibsonomy.org/bibtex/241020afd8d7c1c7c951c249a6308087e/hlwoodcock}, citeulike-article-id = {569619}, interhash = {ecf42faea99a50c2b98e3ec44e1e06e6}, intrahash = {41020afd8d7c1c7c951c249a6308087e}, journal = {JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, keywords = {bibtex-import}, number = 16, pages = {3858--3866}, priority = {2}, timestamp = {2006-06-16T05:03:46.000+0200}, title = {Walden-inversion-enforced transition-state stabilization in a protein tyrosine phosphatase}, volume = 120, year = 1998 }