3FO9

Crystal structure of aldolase antibody 33F12 Fab' in complex with hapten 1,3-diketone

Summary for 3FO9

• Entry DOI: 10.2210/pdb3fo9/pdb
• Related: 1axt
• Descriptor: Immunoglobulin IGG2A - light chain, Immunoglobulin IGG2A - heavy chain, 5-{[4-(5-methyl-3-oxohex-4-en-1-yl)phenyl]amino}-5-oxopentanoic acid, ... (4 entities in total)
• Functional Keywords: aldolase antibody, enamine intermediate, amine catalysis, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 4
• Total formula weight: 96580.10

Authors

Zhu, X.,Wilson, I.A. (deposition date: 2008-12-29, release date: 2009-12-22, Last modification date: 2024-10-30)

Primary citation

Zhu, X.,Tanaka, F.,Lerner, R.A.,Barbas, C.F.,Wilson, I.A.
Direct observation of an enamine intermediate in amine catalysis
J.Am.Chem.Soc., 131:18206-18207, 2009

PubMed Abstract: An enamine intermediate is believed to be the central feature of biological catalysts, such as aldolases and small molecule amine organocatalysts. Despite decades of investigation of naturally occurring aldolase enzymes and recent studies on designed aldolase antibodies and organocatalysts, direct structural observation of an enamine intermediate has proven to be rare. Herein, we report the observation of a stable enamine intermediate in the crystal structure of an aldolase antibody 33F12 in complex with a 1,3-diketone derivative. This enamine complex structure provides strong evidence that fewer residues are essential for amine catalysis within the hydrophobic environments of this catalytic antibody than speculated for natural aldolase enzymes and should serve to guide future studies aimed at the rational design of these types of catalysts, as well as organocatalysts. Indeed, enamine catalysis in proteins might be more simplistic than previously imagined.

PubMed: 19968282
DOI: 10.1021/ja907271a

Experimental method

X-RAY DIFFRACTION (1.9 Å)