Crystal structure of a Flp recombinase-Holliday junction complex: Assemblyof an active oligomer by helix swapping

The crystal structure of a Flp recombinase tetramer bound to a Holliday jun ction intermediate has been determined at 2.65 Angstrom resolution. Only on e of Flp's two domains, containing the active site, is structurally related to other lambda integrase family site-specific recombinases, such as Ore. The Flp active site differs, however, in that the helix containing the nucl eophilic tyrosine is domain swapped, such that it cuts its DNA target in tr ans. The Flp tetramer displays pseudo fourfold symmetry matching that of th e square planar Holliday junction substrate. This tetramer is stabilized by additional novel trans interactions among monomers. The structure illustra tes how mechanistic unity is maintained on a chemical level while allowing for substantial variation on the structural level within a family of enzyme s.