INSIGHTS INTO ANTIBODY CATALYSIS - STRUCTURE OF AN OXYGENATION CATALYST AT 1.9-ANGSTROM RESOLUTION

The x-ray crystal structures of the sulfide oxidase antibody 28B4 and of antibody 28B4 complexed with hapten have been solved at 2.2-Angstro m and 1.9-Angstrom resolution, respectively. To our knowledge, these s tructures are the highest resolution catalytic antibody structures to date and provide insight into the molecular mechanism of this antibody -catalyzed monooxygenation reaction. Specifically, the data suggest th at entropic restriction plays a fundamental role in catalysis through the precise alignment of the thioether substrate and oxidant. The anti body active site also stabilizes developing charge on both sulfur and periodate in the transition state via cation-pi and electrostatic inte ractions, respectively. In addition to demonstrating that the active s ite of antibody 28B4 does indeed reflect the mechanistic information p rogrammed in the aminophosphonic acid hapten, these high-resolution st ructures provide a basis for enhancing turnover rates through mutagene sis and improved hapten design.