( minutes inside the human body a cocai...)High resolution 'snapshots' detail dynamics of a cocaine antibody

Generated by x-ray crystallography, pictures of the conformational changes that occur during the antibody's complete catalytic cycle show the molecular basis for catalysis and reveal possible mutations that could increase catalytic proficiency. This, Zhu pointed out, provides a foundation for the humanization and mutagenesis of the antibody to enhance its cocaine-hydrolyzing activity and make future human clinical trials feasible. "Given the fact that catalytic antibodies have been produced with the same levels of efficiency as natural enzymes, it seems well within the realm of possibility," he added.

To reach this ambitious goal, however, it may be necessary to explore new incremental approaches for optimizing the efficiency of such catalytic activity. Novel functional groups could be introduced into first generation antibody catalysts by multiple rounds of mutagenesis and selection to produce improvements. In essence, this would allow scientists to dramatically accelerate the evolutionary process, producing improvements in the immune system in weeks or months that previously took billions of years.

"The structural insights into antibody catalysis that we have shown with 7A1 Fab' are critical for any future improvement of effective biocatalysts," Zhu said. "One of the main goals of our lab has been to focus on catalytic antibodies that will have a direct impact on public health issues. With the snapshots of the complete cycle of the cocaine antibody catalytic reaction, we have shed new light on the sequence of events in an antibody-mediated reaction and provided a rare glimpse of the structural dynamics involved. With this information, it's possible to move onto the next step in the development of a treatment for cocaine abuse and addiction."'"/>

Source:Scripps Research Institute