ArticleProceedings of the National Academy of Sciences of the United States of America2013
Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
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- Good Vibrations Report on the DNA Quadruplex Binding of an Excited State Amplified Ruthenium Polypyridyl IR Probe.Journal of the American Chemical Society · 2023Article
- Proton transfer reactions: From photochemistry to biochemistry and bioenergetics.BBA advances · 2023Article
- High throughput and quantitative enzymology in the genomic era.Current opinion in structural biology · 2021Review
- Novel protein science enabled by total chemical synthesis.Protein science : a publication of the Protein Society · 2019Review
- Rapid Sampling of Hydrogen Bond Networks for Computational Protein Design.Journal of chemical theory and computation · 2018Article
- Hydrogen Atomic Positions of O-H···O Hydrogen Bonds in Solution and in the Solid State: The Synergy of Quantum Chemical Calculations with ¹H-NMR Chemical Shifts and X-ray Diffraction Methods.Molecules (Basel, Switzerland) · 2017Review
- Dissecting Proton Delocalization in an Enzyme's Hydrogen Bond Network with Unnatural Amino Acids.Biochemistry · 2015Article
- Joint neutron crystallographic and NMR solution studies of Tyr residue ionization and hydrogen bonding: Implications for enzyme-mediated proton transfer.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Quantum delocalization of protons in the hydrogen-bond network of an enzyme active site.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Revealing the functional states in the active site of BLUF photoreceptors from electrochromic shift calculations.The journal of physical chemistry. B · 2014Article
- Ground-state proton transfer kinetics in green fluorescent protein.Biochemistry · 2014Article
- Putative hydrogen bond to tyrosine M208 in photosynthetic reaction centers from Rhodobacter capsulatus significantly slows primary charge separation.The journal of physical chemistry. B · 2014Article
- Live-cell vibrational imaging of choline metabolites by stimulated Raman scattering coupled with isotope-based metabolic labeling.The Analyst · 2014Article
- Uncovering the determinants of a highly perturbed tyrosine pKa in the active site of ketosteroid isomerase.Biochemistry · 2013Article
- Thermodynamic framework for identifying free energy inventories of enzyme catalytic cycles.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Hydrogen bond networks are key elements of protein structure and function but have been challenging to study within the complex protein environment. We have carried out in-depth interrogations of the proton transfer equilibrium within a hydrogen bond network formed to bound phenols in the active site of ketosteroid isomerase. We systematically varied the proton affinity of the phenol using differing electron-withdrawing substituents and incorporated site-specific NMR and IR probes to quantitatively map the proton and charge rearrangements within the network that accompany incremental increases in phenol proton affinity. The observed ionization changes were accurately described by a simple equilibrium proton transfer model that strongly suggests the intrinsic proton affinity of one of the Tyr residues in the network, Tyr16, does not remain constant but rather systematically increases due to weakening of the phenol-Tyr16 anion hydrogen bond with increasing phenol proton affinity. Using vibrational Stark spectroscopy, we quantified the electrostatic field changes within the surrounding active site that accompany these rearrangements within the network. We were able to model these changes accurately using continuum electrostatic calculations, suggesting a high degree of conformational restriction within the protein matrix. Our study affords direct insight into the physical and energetic properties of a hydrogen bond network within a protein interior and provides an example of a highly controlled system with minimal conformational rearrangements in which the observed physical changes can be accurately modeled by theoretical calculations.
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