Alternative DNA structures: G4 DNA in cells: itae missa est?

conformational differences to the starting model, demonstrating the well-known need for allowing backbone flexibility in the design procedure. More information, however, would have been gained from a structure with bound substrate or transition state analog. Interestingly, both adenosine deaminase and the bacterial phosphotriesterase, which is known to hydrolyze organophosphate triesters with considerable rate enhancement, belong to the same metallodependent hydrolase superfamily. However, in contrast to the binuclear zinc-containing phosphotriesterase10, the designed adenosine deaminase uses only a single zinc coordination site. A substrate-bound structure might help to distinguish between the possible mechanisms discussed in the paper as well as provide further insights for future design efforts. Taken together, computational enzyme redesign as presented by Khare et al.6 is clearly useful for the construction of new and applicable metalloenzymes. In addition, it helps to test our (limited) understanding of enzyme mechanisms, thus improving future designs. Similarly, structural analysis and directed evolution provide much needed feedback for computational design approaches. ■ Birte Höcker is at the Max Planck Institute for Developmental Biology, Tübingen, Germany. e-mail: [email protected]