THE ROLE OF TRP84 IN CATALYTIC POWER AND THE SPECIFICITY OF ACHE

The structure-function relationship between the alkaloids physostigmin e, physovenine and the three structurally related compounds were inves tigated by employing kinetic studies and molecular modeling. Crystallo graphic data from the X-ray conformation of the Torpedo californica ac etylcholinesterase complex together with the transition state analog i nhibitor m-(N, N, N,-Trimethylammonio) trifluoroacetophenone (TMTFA) w as used as template onto which inhibitors were superimposed. Among the structural elements of the active site, TRP84 residue shows a versati le role. In fact, its aromatic electrons not only can be employed in p i-cation interactions, as is the case for ACh, but they can also provi de a polarizable surface for van der Waals and London interactions. (C ) 1998 Elsevier Science B.V. All rights reserved.