BY CRACKING an old biochemical puzzle, two German crystallographers have struck a blow against the “superbugs” now sweeping the world’s hospitals. The team has established the detailed structure of vancomycin, the antibiotic that forms the last line of defence against the drug-resistant bacteria, and so may have paved the way for more effective antibiotic designs.
Vancomycin has defied previous attempts to establish its structure because it is too complicated to probe with orthodox techniques. To solve this problem, Martina Schäfer and George Sheldrick of the University of Göttingen in Germany used a standard technique called X-ray crystallography. However, to obtain images with the required resolution, the researchers had to work with unusually powerful X-rays produced by a synchrotron device in Hamburg, which the university shares with the European Molecular Biology Laboratory.
Crystallographers can decipher details of a crystalline compound’s molecular structure by bombarding it with X-rays and examining the patterns the diffracted X-rays make as they bounce out of the crystal. To make sense of the crystallographic information on vancomycin, Sheldrick’s team had to run it through a specially written computer program.
Earlier research had shown that vancomycin works by binding to and disrupting polypeptide “tentacles” that extend from glycopeptides in the cell walls of bacteria. But in a fresh twist to the tale, the team showed that vancomycin does this in a Samson-like fashion: by holding apart two polypeptide strands that would normally bind neighbouring glycopeptides together. Denied their ability to link up, the polypeptides leave a weak point in the bacterial cell wall, which subsequently bursts open (Structure, vol 4, p 1509).
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