New 'Twist' In Proteins Offers Possible Route To Improved A...( DURHAM N.C. -- Biochemists using X-ra...)

DURHAM, N.C. -- Biochemists using X-ray crystallography to figure out the structure of an enzyme critical to the growth of many bacteria have discovered an extremely unusual "left-handed" spiral structure in the molecule.

The finding suggests the possibility of a new kind of antibiotic that could recognize the unusual structure, jam the enzyme and kill bacteria. Bacteria would find it extremely difficult, if not impossible, to develop resistance to such a drug, since the enzyme, called LpxA, is necessary to bacterial growth, the scientists said.

Bacterial resistance to antibiotics has become an important health problem and one that has defied solution, since bacteria can so readily adapt to the current generation of antibiotics.

The researchers, who published their findings in the Nov. 10 issue of the journal Science, are Christian Raetz, chairman and professor in the Duke University Medical Center department of biochemistry, and Steven Roderick, assistant professor at the Albert Einstein College of Medicine department of biochemistry. Their research is sponsored by the National Institutes of Health.

In the report, Raetz and Roderick reported X-ray crystallographic studies of LpxA from the common gut bacterium Escherichia coli. The LpxA enzyme catalyzes the first step in synthesis of the lipid that makes up the outer membrane of the bacteria. Specifically, LpxA catalyzes the transfer of the 14-carbon fatty acid hydroxymyristate, to the acceptor, UDP-N-acetyl glucosamine, and functions as the first step of lipid A biosynthesis. Lipid A serves as the outermost coat of bacteria like E. coli. Thus, LpxA is "essential for bacterial growth as well as the maintenance of the permeability barrier function of the outer membrane," the scientists said.

Like all protein enzymes, LpxA consists of a long chain of amino acids that folds itself into the compact structure, which constitutes the functioning enzyme. These folde
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Contact: Dennis Meredith
meredithd@mail01.adm.duke.edu
919-681-8054
Duke University
29-Apr-1996