Multimeric structure of a subfamily III haloalkane dehalogenase-like enzyme solved by combination of cryo-EM and x-ray crystallography.

Haloalkane dehalogenase (HLD) enzymes employ an S 2 nucleophilic substitution mechanism to erase halogen substituents in diverse organohalogen compounds. Subfamily I and II HLDs are well-characterized enzymes, but the mode and purpose of multimerization of subfamily III HLDs are unknown. Here we probe the structural organization of DhmeA, a subfamily III HLD-like enzyme from the archaeon Haloferax mediterranei, by combining cryo-electron microscopy (cryo-EM) and x-ray crystallography.

Tools for computational design and high-throughput screening of therapeutic enzymes.

Therapeutic enzymes are valuable biopharmaceuticals in various biomedical applications. They have been successfully applied for fibrinolysis, cancer treatment, enzyme replacement therapies, and the treatment of rare diseases. Still, there is a permanent demand to find new or better therapeutic enzymes, which would be sufficiently soluble, stable, and active to meet specific medical needs.