ArticleBiochemistry2015
Dissecting Proton Delocalization in an Enzyme's Hydrogen Bond Network with Unnatural Amino Acids.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Noncanonical Amino Acids: Bringing New-to-Nature Functionalities to Biocatalysis.Chemical reviews · 2024Review
- Understanding the role of negative charge in the scaffold of an artificial enzyme for COJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024Article
- Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion.Chemical reviews · 2024Review
- Photosynthetic reaction center variants made via genetic code expansion show Tyr at M210 tunes the initial electron transfer mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Development and Testing of Force Field Parameters for Phenylalanine and Tyrosine Derivatives.Frontiers in molecular biosciences · 2020Article
- Perturbation of Short Hydrogen Bonds in Photoactive Yellow Protein via Noncanonical Amino Acid Incorporation.The journal of physical chemistry. B · 2019Article
- Formal Reduction Potentials of Difluorotyrosine and Trifluorotyrosine Protein Residues: Defining the Thermodynamics of Multistep Radical Transfer.Journal of the American Chemical Society · 2017Article
- A Critical Test of the Electrostatic Contribution to Catalysis with Noncanonical Amino Acids in Ketosteroid Isomerase.Journal of the American Chemical Society · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Extended hydrogen bond networks are a common structural motif of enzymes. A recent analysis proposed quantum delocalization of protons as a feature present in the hydrogen bond network spanning a triad of tyrosines (Y(16), Y(32), and Y(57)) in the active site of ketosteroid isomerase (KSI), contributing to its unusual acidity and large isotope shift. In this study, we utilized amber suppression to substitute each tyrosine residue with 3-chlorotyrosine to test the delocalization model and the proton affinity balance in the triad. X-ray crystal structures of each variant demonstrated that the structure, notably the O-O distances within the triad, was unaffected by 3-chlorotyrosine substitutions. The changes in the cluster's acidity and the acidity's isotope dependence in these variants were assessed via UV-vis spectroscopy and the proton sharing pattern among individual residues with (13)C nuclear magnetic resonance. Our data show pKa detuning at each triad residue alters the proton delocalization behavior in the H-bond network. The extra stabilization energy necessary for the unusual acidity mainly comes from the strong interactions between Y(57) and Y(16). This is further enabled by Y(32), which maintains the right geometry and matched proton affinity in the triad. This study provides a rich picture of the energetics of the hydrogen bond network in enzymes for further model refinement.
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