Catalytic antibodies and other biomimetic catalysts

Stevenson, James D.; Thomas, Neil R.

doi:10.1039/b006389o

Cited by 67 publications

(23 citation statements)

References 244 publications

(206 reference statements)

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“…7 However, even for the catalytic antibodies, the mechanism of the transition-state stabilization is not fully understood, because most of the structural information has been derived from Xray crystallographic analyses of catalytic antibodies complexed with their TSAs. 1,8 Therefore, little is known about the antibody-substrate complexes so far, [9][10][11]19 apparently because it is difficult to retain the substrate-bound state of the catalytic antibody during the observation, without the conversion of the substrate to the product. In addition, the catalytic contributions of the protein dynamics are not well understood for catalytic antibodies, in spite of the fact that some previous studies suggested that the dynamics play important roles in the catalytic activity, 13 and that the dynamic nature of antibodies has frequently been observed within the complementarity-determining regions (CDRs).…”

Section: Introductionmentioning

confidence: 98%

“…1,2 The application of catalytic antibodies is not limited to the field of chemical synthesis, 3 but has expanded to several medical areas, including cancer therapy, 4 inflammation treatment, 5 and the production of transgenic herbicide-tolerant plants. 18 In addition to these applications, catalytic antibodies provide a better opportunity to understand the molecular mechanisms of biocatalysts.…”

Section: Introductionmentioning

confidence: 99%

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Structural Basis of the Transition-state Stabilization in Antibody-catalyzed Hydrolysis

Sakakura

Takahashi

Shimba

et al. 2007

Journal of Molecular Biology

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Structural Basis of the Transition-state Stabilization in Antibody-catalyzed Hydrolysis

Sakakura

Takahashi

Shimba

et al. 2007

Journal of Molecular Biology

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“…1,2 Catalytic antibodies are obtained by immunization against small molecule haptens. The main strategy consists in designing haptens that mimic the transition state of the targeted reaction by shape and charge.…”

Section: Introductionmentioning

confidence: 99%

Expression Improvement and Mechanistic Study of the Retro-Diels-Alderase Catalytic Antibody 10F11 by Site-directed Mutagenesis

Zheng

Goddard

Baumann

et al. 2004

Journal of Molecular Biology

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“…In light of the many different reactions that have been catalyzed by antibodies [5], the immunoglobulin scaffold is clearly a versatile starting point for enzyme design. Nevertheless, rather than providing many distinct structural solutions to a given recognition problem, as might have been expected from the enormous sequence diversity of the primary repertoire, antibodies appear to use a relatively limited number of strategies for binding certain classes of ligand.…”

mentioning

confidence: 99%

Promiscuity in Antibody Catalysis: Esterolytic Activity of the Decarboxylase 21D8

Backes

Hotta

Hilvert

2003

Helvetica Chimica Acta

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Dedicated to Jack D. Dunitz on the occasion of his 80th birthdayThe high structural similarity of decarboxylase antibody 21D8 and esterase antibody 48G7 suggests that 21D8 might also possess hydrolytic activity. Kinetic investigations show that 21D8 does promote the selective hydrolysis of methyl 4-nitrophenyl carbonate and sodium 4-(acetoxy)benzenesulfonate with catalytic proficiencies (k cat /K m )/k un of ca. 10 5 m À1. The ability of 21D8 to accelerate a reaction for which it was not developed suggests that certain antibody scaffolds are intrinsically predisposed toward catalysis, a property that can be enhanced and refined during affinity maturation in response to a transition-state analog. At the same time, however, the restricted structural diversity of the immune system may ultimately limit the catalytic efficiency that can be achieved.1. Introduction. ± The immune system provides the largest combinatorial library for molecular recognition in nature. It has been estimated that the primary immunoglobulin repertoire contains ca. 10 8 different antibodies [1], and that this diversity is further expanded by several orders of magnitude through the process of somatic hypermutation [2], allowing high affinity recognition of virtually any antigen.The selectivity and diversity of the immune system have been exploited for the generation of tailored antibody receptors for many applications, including catalysis [3] [4]. The latter is achieved when a small molecule carrying chemical information about a particular reaction mechanism, such as a stable analog of a transition state, is used to induce an immune response. Catalytic antibodies, with their programmable activities, have proved to be valuable model systems for analyzing the mechanism and evolution of catalysis in proteins.In light of the many different reactions that have been catalyzed by antibodies [5], the immunoglobulin scaffold is clearly a versatile starting point for enzyme design. Nevertheless, rather than providing many distinct structural solutions to a given recognition problem, as might have been expected from the enormous sequence diversity of the primary repertoire, antibodies appear to use a relatively limited number of strategies for binding certain classes of ligand. The high degree of structural similarity in hydrolytic antibodies generated in response to aryl phosphonates and phosphonamides is a case in point [6]. Even haptens that are less obviously related can induce homologous active sites. For example, 2-(acetamido)naphthalene-1,5-disulfonate (1) and 4-nitrophenyl phosphonate 2, which both contain tetrahedral anions and hydrophobic aryl groups but are otherwise dissimilar, gave rise to antibodies that bear a striking resemblance to one another [7] (Fig. 1).

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Catalytic antibodies and other biomimetic catalysts

Cited by 67 publications

References 244 publications

Structural Basis of the Transition-state Stabilization in Antibody-catalyzed Hydrolysis

Structural Basis of the Transition-state Stabilization in Antibody-catalyzed Hydrolysis

Expression Improvement and Mechanistic Study of the Retro-Diels-Alderase Catalytic Antibody 10F11 by Site-directed Mutagenesis

Promiscuity in Antibody Catalysis: Esterolytic Activity of the Decarboxylase 21D8

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