ArticleJournal of molecular biology2016
Tungstate as a Transition State Analog for Catalysis by Alkaline Phosphatase.
Article in Journal of molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Zero-shot design of abioRxiv : the preprint server for biology · 2026Article
- ExploringPlants (Basel, Switzerland) · 2024Article
- Decoupling of catalysis and transition state analog binding from mutations throughout a phosphatase revealed by high-throughput enzymology.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Second-Shell Residues Contribute to Catalysis by Predominately Preorganizing the Apo State in PafA.Journal of the American Chemical Society · 2023Article
- Identification of multidentate tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors that simultaneously access the DNA, protein and catalytic-binding sites by oxime diversification.RSC chemical biology · 2023Article
- Monitoring protein conformational changes using fluorescent nanoantennas.Nature methods · 2022Article
- Protein Mass-Modulated Effects in Alkaline Phosphatase.Biochemistry · 2021Article
- Predicting Protein-Polymer Block Copolymer Self-Assembly from Protein Properties.Biomacromolecules · 2019Article
- Quantum Mechanical/Molecular Mechanical Analysis of the Catalytic Mechanism of Phosphoserine Phosphatase.Molecules (Basel, Switzerland) · 2018Article
- Intermolecular correlations are necessary to explain diffuse scattering from protein crystals.IUCrJ · 2018Article
- Analysis of Phosphoryl-Transfer Enzymes with QM/MM Free Energy Simulations.Methods in enzymology · 2018Article
- Catalytic scaffolds for phosphoryl group transfer.Current opinion in structural biology · 2016Review
- Mechanistic and Evolutionary Insights from Comparative Enzymology of Phosphomonoesterases and Phosphodiesterases across the Alkaline Phosphatase Superfamily.Journal of the American Chemical Society · 2016Article
- Substrate and Transition State Binding in Alkaline Phosphatase Analyzed by Computation of Oxygen Isotope Effects.Journal of the American Chemical Society · 2016Article
- QM/MM Analysis of Transition States and Transition State Analogues in Metalloenzymes.Methods in enzymology · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
The catalytic mechanisms underlying Escherichia coli alkaline phosphatase's (AP) remarkable rate enhancement have been probed extensively. Past work indicated that whereas the serine nucleophile (Ser102) electrostatically repels the product phosphate, another oxyanion, tungstate, binds more strongly in the presence of Ser102. These results predict a covalent bond between the serine nucleophile and tungstate, a model that we test herein. The crystal structure of tungstate-bound alkaline phosphatase provides evidence for a covalent adduct model and further shows that the ligand adopts trigonal bipyramidal geometry, which is infrequently observed for tungstate in small molecules and other active sites but mirrors the geometry of the presumed phosphoryl transfer transition state. The AP active site is known to stabilize another oxyanion, vanadate, in trigonal bipyramidal geometry, but the extent to which binding of either ligand reproduces the energetics of the transition state cannot be deduced from structural inspection alone. To test for transition state analog behavior, we determined the relationship between catalytic activity and affinity for tungstate and vanadate for a series of 20 AP variants. Affinity and activity were highly correlated for tungstate (r(2) = 0.89) but not vanadate (r(2) = 0.23), indicating that the tungstate•AP complex may better mimic this enzyme's transition state properties. The results herein suggest that tungstate will be a valuable tool for further dissecting AP catalysis and may prove helpful in mechanistic studies of other phosphoryl transfer enzymes.
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