Structural parsimony in endonuclease active sites: should the number of homing endonuclease families be redefined?

Homing endonucleases are classified into four families based on active site sequence motifs, Through structural comparisons we have found structural s imilarities between the endonuclease domain of colicin E9, an H-N-H motif-c ontaining enzyme, acid both the non-specific nuclease from Serratia and I-P poI, a His-Cys box-containing homing endonuclease. Our comparison identifie s conservation at the heart of all three enzyme active sites and so argues for a re-classification of H-NH and His-Cys box homing endonucleases as a s ingle family. We suggest the 'beta beta alpha-Me family' of homing enzymes to reflect the three elements of secondary structure and the metal ion that define the motif. (C) 1999 Federation of European Biochemical Societies.