ArticleJournal of the American Chemical Society2007
Routes to covalent catalysis by reactive selection for nascent protein nucleophiles.
Article in Journal of the American Chemical Society, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Chemical neighborhood exploration for substrate discovery in biocatalysis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multiscale computation delivers organophosphorus reactivity and stereoselectivity to immunoglobulin scavengers.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Catalytic antibody (catabody) platform for age-associated amyloid disease: From Heisenberg's uncertainty principle to the verge of medical interventions.Mechanisms of ageing and development · 2020Review
- Robotic QM/MM-driven maturation of antibody combining sites.Science advances · 2016Article
- Deficient synthesis of class-switched, HIV-neutralizing antibodies to the CD4 binding site and correction by electrophilic gp120 immunogen.AIDS (London, England) · 2014Article
- Metal-dependent amyloid β-degrading catalytic antibody construct.Journal of biotechnology · 2014Article
- Chemically programmed antibodies.Trends in biotechnology · 2014Review
- Role of κ→λ light-chain constant-domain switch in the structure and functionality of A17 reactibody.Acta crystallographica. Section D, Biological crystallography · 2014Article
- CD4 binding determinant mimicry for HIV vaccine design.Frontiers in immunology · 2012Article
- Reactibodies generated by kinetic selection couple chemical reactivity with favorable protein dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- A human germ line antibody light chain with hydrolytic properties associated with multimerization status.The Journal of biological chemistry · 2009Article
- Phage display on the base of filamentous bacteriophages: application for recombinant antibodies selection.Acta naturae · 2009Article
- Covalent binding antibodies suppress advanced glycation: on the innate tier of adaptive immunity.Acta naturae · 2009Article
- Reactive immunization suppresses advanced glycation and mitigates diabetic nephropathy.Journal of the American Society of Nephrology : JASN · 2009Article
- Article
- Catalytic bioscavengers against toxic esters, an alternative approach for prophylaxis and treatments of poisonings.Acta naturae · 2009Article
- Antibodies-antidotes against organophosphorus compounds.Doklady. Biochemistry and biophysicsArticle
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Authors and funding
14 authors.
Funding
Abstract
Reactivity-based selection strategies have been used to enrich combinatorial libraries for encoded biocatalysts having revised substrate specificity or altered catalytic activity. This approach can also assist in artificial evolution of enzyme catalysis from protein templates without bias for predefined catalytic sites. The prevalence of covalent intermediates in enzymatic mechanisms suggests the universal utility of the covalent complex as the basis for selection. Covalent selection by phosphonate ester exchange was applied to a phage display library of antibody variable fragments (scFv) to sample the scope and mechanism of chemical reactivity in a naive molecular library. Selected scFv segregated into structurally related covalent and noncovalent binders. Clones that reacted covalently utilized tyrosine residues exclusively as the nucleophile. Two motifs were identified by structural analysis, recruiting distinct Tyr residues of the light chain. Most clones employed Tyr32 in CDR-L1, whereas a unique clone (A.17) reacted at Tyr36 in FR-L2. Enhanced phosphonylation kinetics and modest amidase activity of A.17 suggested a primitive catalytic site. Covalent selection may thus provide access to protein molecules that approximate an early apparatus for covalent catalysis.
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