Work

Direct Observation of an Enamine Intermediate in Amine Catalysis

Year: 2009

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja907271a

Authors: Xueyong Zhu, Fujie Tanaka, Richard A. Lerner, Carlos F. Barbas III, Ian A. Wilson

Institution: Scripps Research Institute

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Cancer Institute, National Institute of Allergy and Infectious Diseases

Awards: G1533553031, G2269286100, G3830686844, G5205296000, CONSEQUENCES OF ENDOGENOUS RETROVIRAL EXPRESSION