3FO0

Crystal structure of hapten complex of catalytic elimination antibody 13G5 (wild-type)

Summary for 3FO0

• Entry DOI: 10.2210/pdb3fo0/pdb
• Related: 2GJZ 2GK0 3FO1 3FO2
• Descriptor: Catalytic antibody Fab 13G5 kappa light chain chimera, Catalytic antibody Fab 13G5 IgG2b heavy chain chimera, 5-[(2-AMINO-1H-BENZIMIDAZOL-6-YL)AMINO]-5-OXOPENTANOIC ACID, ... (5 entities in total)
• Functional Keywords: immunoglobulin, catalytic antibody, chimeric fab, hapten complex, acid base catalysis, proton transfer, immunoglobulin domain, immune system
• Biological source: Mus musculus, Homo sapiens (Mouse, Human); More
• Total number of polymer chains: 2
• Total formula weight: 48653.36

Authors

Debler, E.W.,Wilson, I.A. (deposition date: 2008-12-27, release date: 2009-11-10, Last modification date: 2023-09-06)

Primary citation

Debler, E.W.,Muller, R.,Hilvert, D.,Wilson, I.A.
An aspartate and a water molecule mediate efficient acid-base catalysis in a tailored antibody pocket.
Proc.Natl.Acad.Sci.USA, 106:18539-18544, 2009

PubMed Abstract: Design of catalysts featuring multiple functional groups is a desirable, yet formidable goal. Antibody 13G5, which accelerates the cleavage of unactivated benzisoxazoles, is one of few artificial enzymes that harness an acid and a base to achieve efficient proton transfer. X-ray structures of the Fab-hapten complexes of wild-type 13G5 and active-site variants now afford detailed insights into its mechanism. The parent antibody preorganizes Asp(H35) and Glu(L34) to abstract a proton from substrate and to orient a water molecule for leaving group stabilization, respectively. Remodeling the environment of the hydrogen bond donor with a compensatory network of ordered waters, as seen in the Glu(L34) to alanine mutant, leads to an impressive 10(9)-fold rate acceleration over the nonenzymatic reaction with acetate, illustrating the utility of buried water molecules in bifunctional catalysis. Generalization of these design principles may aid in creation of catalysts for other important chemical transformations.

PubMed: 19846764
DOI: 10.1073/pnas.0902700106

Experimental method

X-RAY DIFFRACTION (2.5 Å)