Vertex Pharmaceuticals Researchers Report Three-Dimensional Structure Of Hepatitis C Helicase Enzyme; Report In...( epatitis C NS3helicase complexed wi...)

epatitis C NS3 helicase complexed with a single-stranded DNA oligonucleotide using X-ray crystallography. This biophysical technique determines accurately the position of every atom of the complex. Vertex used X-ray diffraction data with the aid of computational techniques to construct a high-resolution (2.2 angstroms) electron density map of the complex. The map reveals the nucleic acid-binding site, as well as the previously described ATP-binding site that drives the enzyme's activity, amid three distinct structural domains of the NS3 helicase. The structure yields important clues regarding the mechanism by which helicase enzymes unravel double-stranded nucleic acid helices.

"The atomic structure of the HCV helicase enzyme shows several unique features that we believe will provide opportunities to accelerate our ongoing efforts to design potent and specific drugs against hepatitis C," said Dr. Paul Caron, Vertex biophysicist and also an author of the Structure paper. "In addition to providing information on a key target for therapeutic intervention, the structural data we have unveiled also suggests a possible mechanism of nucleic acid unwinding for this and related helicases. "

"The solution of the HCV helicase structure complements the solution of the three-dimensional atomic structure of another drug target, HCV protease, reported by Vertex researchers in 1996," added Dr. Vicki L. Sato, Senior Vice President of Research and Development and Chief Scientific Officer of Vertex. "Given the combination therapy approach now being advocated and developed for treatment of many viral diseases, pursuing multiple discovery targets against HCV enhances our competitive position in the future market for HCV therapies."

Discovered in 1989, HCV causes chronic inflammation in the liver. In a majority of patients, HCV establishes a chronic infection that can persist for decades and eventually lead to c
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Contact: Michael Partridge
partridge@vpharm.com
(617) 577-6108
Vertex Pharmaceuticals
15-Jan-1998

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