1y18
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(New page: 200px<br /> <applet load="1y18" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y18, resolution 2.80Å" /> '''Fab fragment of cat...)
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Revision as of 07:38, 18 November 2007
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Fab fragment of catalytic elimination antibody 34E4 E(H50)D mutant in complex with hapten
Overview
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.
About this Structure
1Y18 is a Protein complex structure of sequences from Mus musculus, homo sapiens with CL and HAN as ligands. Full crystallographic information is available from OCA.
Reference
Structural origins of efficient proton abstraction from carbon by a catalytic antibody., Debler EW, Ito S, Seebeck FP, Heine A, Hilvert D, Wilson IA, Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):4984-9. Epub 2005 Mar 23. PMID:15788533
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