Diverse structural solutions to catalysis in a family of antibodies

Gigant, B.; Tsumuraya, Takeshi; Fujii, Ikuo; Knossow, M.

doi:10.1016/s0969-2126(00)80028-3

Cited by 22 publications

(19 citation statements)

References 46 publications

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“…The binding free energy difference of 7C8, DDG ITC , was 0.4 kcal Á mol À1 , in contrast to that obtained previously for 6D9, DDG ITC ¼ 1.4 kcal Á mol À1 (Saito et al, 2005). This difference in DDG between 7C8 and 6D9 may be explained by the difference in the binding manner of the CP: the trifluoroacetyl group of CP-F is exposed to the solvent water on the surface of 7C8 while it binds deep in the hydrophobic pocket in 6D9 (Kristensen et al, 1998;Gigant et al, 1999). If in the associated state, the trifluoroacetyl group of CP-F was completely exposed without being affected by 7C8, both DH ITC and TDS ITC of CP-H binding would be similar to those of CP-F binding.…”

contrasting

confidence: 67%

“…Crystal structure analyses have revealed that the two aromatic rings of CP-F are buried in the 6D9 combining site, while only the p-nitrobenzyl group is buried in the 7C8 combining site and the trifluoroacetyl group is exposed to the solvent (Kristensen et al, 1998;Gigant et al, 1999). The binding thermodynamics of 7C8 and 6D9 could be correlated with the data obtained from the crystal structure of the complexes.…”

Section: Discussionmentioning

confidence: 72%

“…Binding free energy changes in the associated (A) and dissociated (D) states due to the substitution of CP-F by CP-H at 300 K (in kcal . The crystal structures clearly indicate that the hydrophobic interactions between CP-F and 7C8 are less than those between CP-F and 6D9 (Kristensen et al, 1998;Gigant et al, 1999). Therefore, the different entropic contributions of 7C8 and 6D9 would be mainly due to the different hydrophobic interactions.…”

Section: Discussionmentioning

confidence: 94%

“…The initial structure of the associated state was prepared as follows. First, the binding complex was prepared by including the Fv region and an additional six residues (i.e., L1-L108 and H1-H114) (the amino acid sequences are numbered according to the consensus nomenclature of Kabat et al (1991)), the antigen CP-F molecule, and 98 nearby waters of crystallization from an X-ray crystal structure of the 7C8 complexed with CP-F refined by Gigant et al (1999) (PDB-ID: 1CT8). Second, the complex in a solution environment was prepared by immersing it in a water sphere .…”

Section: Free Energy Calculations Based On MD Simulationsmentioning

confidence: 99%

“…These antibodies catalyze the hydrolysis of a non-bioactive chloramphenicol monoester derivative to generate a bioactive chloramphenicol (Fujii et al, 1995). The crystal structures of the 6D9 Fab complexed with a derivative of CP-F, and the 7C8 Fab (www.interscience.wiley.com) DOI:10.1002/jmr.958 Research Article * Correspondence to: M. Oda, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho, Shimogamo, Sakyo-ku, Kyoto 606-8522, Japan E-mail: oda@kpu.ac.jp complexed with CP-F were determined (Kristensen et al, 1998;Gigant et al, 1999). In the combining site of 6D9, the two aromatic rings of CP-F were observed to be stacked and buried deep, while in the combining site of 7C8, only the p-nitrobenzyl group was buried and the trifluoroacetyl group of CP-F was exposed to the solvent.…”

Section: Introductionmentioning

confidence: 99%

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Contribution of the trifluoroacetyl group in the thermodynamics of antigen–antibody binding

Oda

Saito

Tsumuraya

et al. 2009

J of Molecular Recognition

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We analyzed the binding of the 7C8 antibody to the chloramphenicol phosphonate antigens-one containing a trifluoroacetyl group (CP-F) and the other containing an acetyl group (CP-H)-by using isothermal titration calorimetry (ITC). The thermodynamic difference due to the substitution of F by H was evaluated using free energy calculations based on molecular dynamics (MD) simulations. We have previously shown that another antibody, namely, 6D9, binds more weakly to CP-H than to CP-F, mainly due to the different hydration free energies of the dissociated state and not due to the unfavorable hydrophobic interactions with the antibody in the bound state. Unlike in the binding of the trifluoroacetyl group with 6D9, in its binding with 7C8, it is exposed to the solvent, as seen in the crystal structure of the complex of 7C8 with CP-F. The thermodynamic analysis performed in this study showed that the binding affinity of 7C8 for CP-H is similar to that for CP-F, but this binding to CP-H is accompanied with less favorable enthalpy and more favorable entropy changes. The free energy calculations indicated that, upon the substitution of F by H, enthalpy and entropy changes in the associated and dissociated states were decreased, but the magnitude of enthalpy and entropy changes in the dissociated state was larger than that in the associated state. The differences in binding free energy, enthalpy, and entropy changes determined by the free energy calculations for the substitution of F by H are in good agreement with the experimental results.

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contrasting

confidence: 67%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 94%

Section: Free Energy Calculations Based On MD Simulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Contribution of the trifluoroacetyl group in the thermodynamics of antigen–antibody binding

Oda

Saito

Tsumuraya

et al. 2009

J of Molecular Recognition

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Catalytic Antibodies Induced by a Zwitterionic Hapten

et al. 2001

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A zwitterionic hapten 4 featuring both positively and negatively charged functional groups was designed and synthesized with the goal of generating catalytic antibodies for the hydrolysis of ester 6 and amide 7. Of the 36 monoclonal antibodies specific to BSA-4 (bovine serum albumin) that were isolated, six accelerated the hydrolysis of 6. Two catalytic antibodies with distinctively different and representative kinetic behaviors were selected for detailed kinetic studies. Whereas H8-2-6F11 showed burst kinetic behavior, which can be attributed to the formation of an acyl intermediate, H8-1-2D5 did not, but it did exhibit high multiple turnover activity. The rate of hydrolysis of 6 catalyzed by H8-1-2D5 followed Michaelis-Menten kinetics; the apparent values of the Michaelis-Menten constant Km and the catalytic constant kcat were 488 microM and 3.5 min(-1), respectively. The catalytic rate enhancement (kcat/kun) observed for H8-1-2D5 was 1.3 x 10(5), which is approximately two orders of magnitude greater than those for monofunctional haptens. Thus H8-1-2D5 compares well in catalytic activity with antibodies isolated by a related approach called heterologous immunization.

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Structure and Function of Catalytic Antibodies

Larsen

Wilson

2008

Protein Science Encyclopedia

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Originally published in: Catalytic Antibodies. Edited by Ehud Keinan. Copyright © 2005 Wiley‐VCH Verlag GmbH & Co. KGaA Weinheim. Print ISBN: 3‐527‐30688‐6 The sections in this article are Introduction Electrostatic Complementarity Anionic Binding Motifs and Ester Hydrolysis Structural Motifs Mechanistic Considerations Mechanistic Pitfalls Structural and Functional Considerations for Hapten Design Anionic Binding Motifs and Control of the Microenvironment in Decarboxylation Anionic Binding Motifs and the Periodate Cofactor in Sulfide Oxygenation Cation Stabilization and Allylic Isomerization Shape Complementarity and Approximation Unimolecular Rearrangements Antibody 1F7 Antibody AZ‐28 Bimolecular Rearrangements and the Diels‐Alder Reaction Retro‐Diels‐Alder Reaction Disfavored exo Diels‐Alder Reaction Endo Diels‐Alder Reactions Shape Complementarity and Control of the Reaction Coordinate Syn ‐Elimination Disfavored Ring Closure Selective Control of a Reactive Carbocation: Antibodies 4C6 and 19A4 Shape Complementarity and Substrate Strain Reactive Amino Acids and the Possibility of Covalent Catalysis Conclusions

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Diverse structural solutions to catalysis in a family of antibodies

Cited by 22 publications

References 46 publications

Contribution of the trifluoroacetyl group in the thermodynamics of antigen–antibody binding

Contribution of the trifluoroacetyl group in the thermodynamics of antigen–antibody binding

Catalytic Antibodies Induced by a Zwitterionic Hapten

Structure and Function of Catalytic Antibodies

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