The structure-function dilemma of the hammerhead ribozyme. Journal Article uri icon

Overview

abstract

  • A powerful approach to understanding protein enzyme catalysis is to examine the structural context of essential amino acid side chains whose deletion or modification negatively impacts catalysis. In principle, this approach can be even more powerful for RNA enzymes, given the wide variety and subtlety of functionally modified nucleotides now available. Numerous recent success stories confirm the utility of this approach to understanding ribozyme function. An anomaly, however, is the hammerhead ribozyme, for which the structural and functional data do not agree well, preventing a unifying view of its catalytic mechanism from emerging. To delineate the hammerhead structure-function comparison, we have evaluated and distilled the large body of biochemical data into a consensus set of functional groups unambiguously required for hammerhead catalysis. By examining the context of these functional groups within available structures, we have established a concise set of disagreements between the structural and functional data. The number and relative distribution of these inconsistencies throughout the hammerhead reaffirms that an extensive conformational rearrangement from the fold observed in the crystal structure must be necessary for cleavage to occur. The nature and energetic driving force of this conformational isomerization are discussed.

publication date

  • January 1, 2005

has subject area

Date in CU Experts

  • March 13, 2015 12:56 PM

Full Author List

  • Blount KF; Uhlenbeck OC

author count

  • 2

citation count

  • 68

Other Profiles

International Standard Serial Number (ISSN)

  • 1056-8700

Electronic International Standard Serial Number (EISSN)

  • 1545-4266

Additional Document Info

start page

  • 415

end page

  • 440

volume

  • 34