X-Ray Crystal Structure Analysis of Recombinant Interleukin-2 and beta-Interferon

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1) Thanks to recombinant DNA technique, certain lymphokines and cytokines such as interleukin-2 (IL-2) and beta-Interferon (IFN-beta) are now available with the amount of sample feasible for crystallographic study. However the crystals obtained from such sample tend to be disordered, twinned and brittle. To cope with such setbacks, we first improved the method of X-ray diffraction data collection by employing synchrotron beam, imaging plate and by improving the softwares.2) We succeeded in growing hexagonal, orthorhombic and monoclimic crystals of IL-2. However even the best of these (the monoclinic crystal) showed marked weakness against radiation damage. Although we were able to show that sulfoxidation of Met 104 was responsible, we could not find effective remedy for this effect.3) We succeeded in growing orthorhombic and hexagonal crystals of IFN-beta. The hexagonal crystal seems almost ideal for full scale structure analysis. Three promising heavy-atom derivatives were found. Attempt at locating the heavy-atom binding sites are under way. We expect to get three-dimensional structure of IFN-beta within a year.