Crystals of a thymidylate synthase mutant offer insights into crystal packing 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 which 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 upon prolonged exposure. We present here an analysis of the possible causes of this transformation based on the crystal structures for two forms of an R178F mutant of this enzyme. We compare these structures to other structures with intermediate cell parameters reported in the literature. There are no large changes in the dimeric structure of TS in these crystal forms. Although there is a large change in the unit cell volume, the molecular contacts in the crystal structures are nearly invariant. The transformation appears to result from concerted small changes in molecular structure and intermolecular contacts. These observations corroborate the general impression that protein structures can accommodate minor changes in sequence or packing wherein the intra and intermolecular interactions are not seriously altered.