STRUCTURAL CONVERGENCE IN THE ACTIVE-SITES OF A FAMILY OF CATALYTIC ANTIBODIES

The x-ray structures of three esterase-like catalytic antibodies ident ified by screening for catalytic activity the entire hybridoma reperto ire, elicited in response to a phosphonate transition state analog (TS A) hapten, were analyzed. The high resolution structures account for c atalysis by transition state stabilization, and in all three antibodie s a tyrosine residue participates in the oxyanion hole. Despite signif icant conformational differences in their combining sites, the three a ntibodies, which are the most efficient among those elicited, achieve catalysis in essentially the same mode, suggesting that evolution for binding to a single TSA followed by screening for catalysis lead to an tibodies with structural convergence.