New catalytic structures from an existing ribozyme.
Although protein enzymes with new catalytic activities can arise from existing scaffolds, less is known about the origin of ribozymes with new activities. Furthermore, mechanisms by which new macromolecular folds arise are not well characterized for either protein or RNA. Here we investigate how readily ribozymes with new catalytic activities and folds can arise from an existing ribozyme scaffold. Using in vitro selection, we isolated 23 distinct kinase ribozymes from a pool of sequence variants of an aminoacylase parent ribozyme. Analysis of these new kinases showed that ribozymes with new folds and biochemical activities can be found within a short mutational distance of a given ribozyme. However, the probability of finding such ribozymes increases considerably as the mutational distance from the parental ribozyme increases, indicating a need to escape the fold of the parent.
Curtis
Edward A
EA
Whitehead Institute for Biomedical Research and Department of Biology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Bartel
David P
DP
D020029:Base Pairing; D001483:Base Sequence; D002384:Catalysis; D004591:Electrophoresis, Polyacrylamide Gel; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship
D016337:RNA, Catalytic