Ab initio structure determination of the lantibiotic mersacidin

The crystal structure of mersacidin, a potential novel antibiotic against m ethicillin- and vancomycin-resistant Staphylococcus aureus strains, has bee n determined by ab initio methods. Despite all crystals being merohedrally twinned, an accurate structural model with an R value of 13.4% has been obt ained at atomic resolution. With six molecules in the asymmetric unit and n o atom heavier than sulfur, the structure corresponds to a protein of 120 a mino acids and is the largest approximately equal-atom unknown structure so lved by direct methods. In the crystal, the molecule assumes a compact fold different from that found by NMR in solution. Comparison of the NCS-relate d molecules reveals regions of variable flexibility. The region highly homo logous to the related antibiotic actagardine is very rigid and possibly def ines an essential building block of this class of new antibacterial substan ces.