Tuning the Phosphoryl Donor Specificity of Dihydroxyacetone Kinase from ATP to Inorganic Polyphosphate. An Insight from Computational Studies
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Other documents of the author: Sánchez Moreno, Israel; Bordes, Isabel; Castillo, Raquel; Ruiz-Pernía, José Javier; Moliner, Vicent; García Junceda, Eduardo
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Title
Tuning the Phosphoryl Donor Specificity of Dihydroxyacetone Kinase from ATP to Inorganic Polyphosphate. An Insight from Computational StudiesAuthor (s)
Date
2015-11-24Publisher
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1661-6596; 1422-0067Bibliographic citation
SÁNCHEZ-MORENO, Israel, et al. Tuning the Phosphoryl Donor Specificity of Dihydroxyacetone Kinase from ATP to Inorganic Polyphosphate. An Insight from Computational Studies. International journal of molecular sciences, 2015, vol. 16, no 11, p. 27835-27849.Type
info:eu-repo/semantics/articlePublisher version
http://www.mdpi.com/1422-0067/16/11/26073/htmlVersion
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Abstract
Dihydroxyacetone (DHA) kinase from Citrobacter freundii provides an easy entry for the preparation of DHA phosphate; a very important C3 building block in nature. To modify the phosphoryl donor specificity of this ... [+]
Dihydroxyacetone (DHA) kinase from Citrobacter freundii provides an easy entry for the preparation of DHA phosphate; a very important C3 building block in nature. To modify the phosphoryl donor specificity of this enzyme from ATP to inorganic polyphosphate (poly-P); a directed evolution program has been initiated. In the first cycle of evolution, the native enzyme was subjected to one round of error-prone PCR (EP-PCR) followed directly (without selection) by a round of DNA shuffling. Although the wild-type DHAK did not show activity with poly-P, after screening, sixteen mutant clones showed an activity with poly-phosphate as phosphoryl donor statistically significant. The most active mutant presented a single mutation (Glu526Lys) located in a flexible loop near of the active center. Interestingly, our theoretical studies, based on molecular dynamics simulations and hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) optimizations, suggest that this mutation has an effect on the binding of the poly-P favoring a more adequate position in the active center for the reaction to take place. [-]
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International journal of molecular sciences, 2015, vol. 16, no 11Rights
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