ArticleBiochemistry2011
Electrostatic fields near the active site of human aldose reductase: 2. New inhibitors and complications caused by hydrogen bonds.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 33 citations in OpenAlex.
- Engineering drug-protein kinetics via intrinsic quantum Stark fields in binding motifs.Journal of molecular modeling · 2025Article
- Critical Evaluation of Polarizable and Nonpolarizable Force Fields for Proteins Using Experimentally Derived Nitrile Electric Fields.Journal of the American Chemical Society · 2024Article
- Protein Dynamics and Enzymatic Catalysis.The journal of physical chemistry. B · 2023Review
- Biomacromolecule-Assisted Screening for Reaction Discovery and Catalyst Optimization.Chemical reviews · 2022Review
- A Novel Small Molecule Neurotrophin-3 Analogue Promotes Inner Ear Neurite Outgrowth and SynaptogenesisFrontiers in cellular neuroscience · 2021Article
- An Ab Initio QM/MM Study of the Electrostatic Contribution to Catalysis in the Active Site of Ketosteroid Isomerase.Molecules (Basel, Switzerland) · 2018Article
- A thiocyanopalladation/carbocyclization transformation identified through enzymatic screening: stereocontrolled tandem C-SCN and C-C bond formation.Chemical science · 2017Article
- Ultrafast dynamics induced by the interaction of molecules with electromagnetic fields: Several quantum, semiclassical, and classical approaches.Structural dynamics (Melville, N.Y.) · 2017Review
- Modeling biophysical and biological properties from the characteristics of the molecular electron density, electron localization and delocalization matrices, and the electrostatic potential.Journal of computational chemistry · 2014Article
- Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Ribonuclease S dynamics measured using a nitrile label with 2D IR vibrational echo spectroscopy.The journal of physical chemistry. B · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Vibrational Stark effect spectroscopy was used to measure electrostatic fields in the hydrophobic region of the active site of human aldose reductase (hALR2). A new nitrile-containing inhibitor was designed and synthesized, and the X-ray structure of its complex, along with cofactor NADP(+), with wild-type hALR2 was determined at 1.3 Å resolution. The nitrile is found to be in the proximity of T113, consistent with a hydrogen bond interaction. Two vibrational absorption peaks were observed at room temperature in the nitrile region when the inhibitor binds to wild-type hALR2, indicating that the nitrile probe experiences two different microenvironments, and these could be empirically separated into a hydrogen-bonded and non-hydrogen-bonded population by comparison with the T113A mutant, in which a hydrogen bond to the nitrile is not present. Classical molecular dynamics simulations based on the structure predict a double-peak distribution in protein electric fields projected along the nitrile probe. The interpretation of these two peaks as a hydrogen bond formation-dissociation process between the probe nitrile group and a nearby amino acid side chain is used to explain the observation of two IR bands, and the simulations were used to investigate the molecular details of this conformational change. Hydrogen bonding complicates the simplest analysis of vibrational frequency shifts as being due solely to electrostatic interactions through the vibrational Stark effect, and the consequences of this complication are discussed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.