Some characteristics of and structural requirements for the interaction of 24,25-dihydrofusidic acid with ribosome - elongation factor g Complexes.

摘要: Fusidic acid inhibits polypeptide chain elongation by binding to the ribosome - factor-G GDP complex and thereby preventing its dissociation. The experiments reported here quantitate interaction of antibiotic [3H]-24,25-dihydrofusidic acid, an active analog fusidic with comples. All components are essential for binding. stoichiometry is ca. 1:1, Ka apparent, as determined equilibrium dialysis, 2.6 times 10-6 M-minus 1. It further shown that GTP equally effective in forming complexes which may bind, whereas GMP beta,gamma-methyleneguanosine triphosphate will not form bind. In order examine structural basis mode action we have considered two activities 21 analogs this antibiotic: ability bind aforementioned ternary stabilize complex. comparative capability were extablished through competition acid. data obtained from these can be summarized follows. (1) C17-20 double bond appears critical both stabilization activities. (2) A carboxyl group vicinity C20 carbon also (3) Modifications other functional groups molecule lead significantly decreased and/or compete complex, but do demonstrate absolute requirements either activity.