ArticleProceedings of the National Academy of Sciences of the United States of America2005
Structural origins of efficient proton abstraction from carbon by a catalytic antibody.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 52 citations in OpenAlex.
- Enhancing aChemical science · 2020Article
- Peptide Side-COOH Groups Have Two Distinct Conformations under Biorelevant Conditions.The journal of physical chemistry letters · 2020Article
- Insights from molecular dynamics simulations for computational protein design.Molecular systems design & engineering · 2017Article
- Kemp Eliminase Activity of Ketosteroid Isomerase.Biochemistry · 2017Article
- Computational strategies for the design of new enzymatic functions.Archives of biochemistry and biophysics · 2015Review
- Bifunctional Mesoporous Carbon Nitride: Highly Efficient Enzyme-like Catalyst for One-pot Deacetalization-Knoevenagel Reaction.Scientific reports · 2015Article
- Article
- Engineering a model protein cavity to catalyze the Kemp elimination.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Computational protein engineering: bridging the gap between rational design and laboratory evolution.International journal of molecular sciences · 2012Review
- Bridging the gaps in design methodologies by evolutionary optimization of the stability and proficiency of designed Kemp eliminase KE59.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Iterative approach to computational enzyme design.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Challenges and advances in validating enzyme design proposals: the case of kemp eliminase catalysis.Biochemistry · 2011Article
- Design of a switchable eliminase.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Optimization of the in-silico-designed kemp eliminase KE70 by computational design and directed evolution.Journal of molecular biology · 2011Article
- Exploring challenges in rational enzyme design by simulating the catalysis in artificial kemp eliminase.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Evaluation and ranking of enzyme designs.Protein science : a publication of the Protein Society · 2010Article
- An aspartate and a water molecule mediate efficient acid-base catalysis in a tailored antibody pocket.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Origin of the activity drop with the E50D variant of catalytic antibody 34E4 for Kemp elimination.The journal of physical chemistry. B · 2009Article
- Testing geometrical discrimination within an enzyme active site: constrained hydrogen bonding in the ketosteroid isomerase oxyanion hole.Journal of the American Chemical Society · 2008Article
- Conformational isomerism can limit antibody catalysis.The Journal of biological chemistry · 2008Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Antibody 34E4 catalyzes the conversion of benzisoxazoles to salicylonitriles with high rates and multiple turnovers. The crystal structure of its complex with the benzimidazolium hapten at 2.5-angstroms resolution shows that a combination of hydrogen bonding, pi stacking, and van der Waals interactions is exploited to position both the base, Glu(H50), and the substrate for efficient proton transfer. Suboptimal placement of the catalytic carboxylate, as observed in the 2.8-angstroms structure of the Glu(H50)Asp variant, results in substantially reduced catalytic efficiency. In addition to imposing high positional order on the transition state, the antibody pocket provides a highly structured microenvironment for the reaction in which the carboxylate base is activated through partial desolvation, and the highly polarizable transition state is stabilized by dispersion interactions with the aromatic residue Trp(L91) and solvation of the leaving group oxygen by external water. The enzyme-like efficiency of general base catalysis in this system directly reflects the original hapten design, in which a charged guanidinium moiety was strategically used to elicit an accurately positioned functional group in an appropriate reaction environment and suggests that even larger catalytic effects may be achievable by extending this approach to the induction of acid-base pairs capable of bifunctional catalysis.
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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.