racemate, behaves as a strong, competitive inhibitor of IS, with a Ki value of 0.36 f 0.05 pM (compare to chorismate K, = 7.0 f 1.3 pM). In contrast, 5 is a weak competitive inhibitor of AS (Ki of 195 f 15 pM; chorismate K,,, = 5.4 f 0.3 pM). The affinity of 5 for IS is not proof that the isomerization catalyzed by this enzyme involves the transition state 4 nor does it suggest whether such a species is cationic or anionic in nature; however, inhibition by 5 is not supportive of a mechanism which requires covalent attachment of the substrate to the enzyme or transient lactonization. That compound 5 is more effective as an inhibitor of IS than of AS, in spite of the homology of the two proteins, may reflect the specificity of AS for ammonia over water as substrate and suggests that the 6-amino analogue of 5 may be a selective inhibitor of AS.