Correlation of structure and activity in ansamycins. Molecular structure of sodium rifamycin SV.
The crystal and molecular structure of the sodium salt of rifamycin SV (clinically known as rifacin) as the monohydrate ethanol solvate has been determined to study the conformation of the ansa chain in unsubstituted rifamycins and also to clarify the metal complexation with rifamycins. The crystals belong to the space group P2(1)2(1)2(1) with cell dimensions (estimated standard deviations in parentheses) of a = 12.061 (2), b = 13.936 (2), and c = 24.731 (4) A. The structure was solved by direct methods and refined to an R factor of 0.069. The conformation of the ansa chain differs from that of other active rifamycins, e.g., rifampcin and rifamycin B at the joining point of the ansa chain to the naphthohydroquinone chromophore. The conformation of the middle part of the ansa chain, which is essential for activity against DNA-dependent RNA polymerase, remains the same. The sodium ion is penta-coordinated and has a trigonal bipyramidal geometry. The intermolecular hydrogen bonding involves O(9), O(10), O(5), and O(6) through water and ethanol molecules. A two-step mode of action of rifamycins has been postulated, and the conformations of antibiotics suitable for penetration of the membrane barrier and that for antibiotic-enzyme complex formation have been suggested.
D000900:Anti-Bacterial Agents / Q000032:analysis*; D003460:Crystallization; D047029:Lactams, Macrocyclic; D008968:Molecular Conformation; D012294:Rifamycins / Q000032:analysis*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D047029:Lactams, Macrocyclic; D012294:Rifamycins; C023808:rifamycin SV