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    Suzanne Jackowski, PhD

    Suzanne Jackowski, PhD

    3-D forms link antibiotic resistance and brain disease

    St. Jude uses computer-generated images of different types of same enzyme to unlock mysteries of antibiotic resistance and a rare form of brain degeneration

    Studies of the 3-D structure of an enzyme used by virtually all living organisms help explain both resistance of some bacteria to certain antibiotics and a rare form of childhood brain degeneration, according to investigators at St. Jude Children’s Research Hospital.  The enzyme, called pantothenate kinase, triggers the first step in the production coenzyme A, a molecule indispensable to all forms of life.

    A report on this study appears in the August 16 issue of the journal Structure.

    The researchers showed how two versions of the enzyme used by different bacteria do the same job, even though the basic strings of amino acids making up their complex 3-D structure are very different. The images also showed that the version used by bacteria called Staphylococcus aureus has a “hole” in its structure that lets an antibiotic called pantothenamide slip in and disrupt its function. But the version used by Pseudomonas aeruginosa does not have such a hole, so it is resistant to the antibiotic.

    The study also showed that the Staphylococcus version of the enzyme  is very similar to the human version, PanK2, according to Suzanne Jackowski, PhD, a member of the St. Jude Department of Infectious Diseases and co-author of the paper. Therefore, the structure of this bacterial enzyme helps to explain how specific mutations in PanK2 disable this enzyme and cause the childhood neurodegeneration disease called pantothenate kinase neurodegeneration. “This holds promise that such insights will one day lead to the development of drugs designed to prevent or treat this disease,” Jackowski said.

    Other authors of the article include co-first authors Bum Soo Hong (University of Toronto, Canada) and Mi Kyung Yun (St. Jude); Yong-Mei Zhang, Shigeru Chohnan, Charles Rock, Stephen White and the senior author, Roberta Leonardi (St. Jude); and Hee-Won Park (University of Toronto).

    This work was supported in part by the National Institutes of Health, a Cancer Center (CORE) Support Grant, and ALSAC.

    November 2006