1Y0L
Catalytic elimination antibody 34E4 in complex with hapten
Summary for 1Y0L
| Entry DOI | 10.2210/pdb1y0l/pdb |
| Related | 1Y18 |
| Descriptor | Catalytic Antibody Fab 34E4 Light chain, Catalytic Antibody Fab 34E4 Heavy chain, 2-AMINO-5,6-DIMETHYL-BENZIMIDAZOLE-1-PENTANOIC ACID, ... (5 entities in total) |
| Functional Keywords | immunoglobulin, catalytic antibody, chimeric fab, hapten complex, immune system |
| Biological source | Mus musculus, Homo sapiens (house mouse, human) More |
| Total number of polymer chains | 8 |
| Total formula weight | 192462.95 |
| Authors | Debler, E.W.,Ito, S.,Heine, A.,Wilson, I.A. (deposition date: 2004-11-15, release date: 2005-04-05, Last modification date: 2024-10-30) |
| Primary citation | Debler, E.W.,Ito, S.,Seebeck, F.P.,Heine, A.,Hilvert, D.,Wilson, I.A. Structural origins of efficient proton abstraction from carbon by a catalytic antibody Proc.Natl.Acad.Sci.USA, 102:4984-4989, 2005 Cited by PubMed 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. PubMed: 15788533DOI: 10.1073/pnas.0409207102 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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