CRYSTALS OF A THYMIDYLATE SYNTHASE MUTANT OFFER INSIGHTS INTO CRYSTALPACKING AND PLASTICITY OF PROTEIN-PROTEIN CONTACTS

Some crystal forms of thymidylate synthase from L. casei exhibit unit sell transformation upon irradiation by X-rays, These forms, all of wh ich occur in the space group P6(1)22, show an elongation in the c cell dimension and in some cases stabilize to a constant cell dimension up on prolonged exposure. We present here an analysis of the possible cau ses of this transformation based on the crystal structures for two for ms of an R178F mutant of this enzyme. We compare these structures to o ther structures with intermediate cell parameters reported in the lite rature. There are no large changes in the dimeric structure of TS in t hese crystal forms. Although there is a large change in the unit cell volume, the molecular contacts in the crystal structures are nearly in variant. The transformation appears to result from concerted small cha nges in molecular structure and intermolecular contacts. These observa tions corroborate the general impression that protein structures can a ccommodate minor changes in sequence or packing wherein the intra and intermolecular interactions are not seriously altered.