|3r1h, resolution 3.15Å ()|
|Gene:||SNRPA (Homo sapiens)|
|Related:||3hhn, 3ivk, 3r1l|
Crystal structure of the Class I ligase ribozyme-substrate preligation complex, C47U mutant, Ca2+ bound
Early life presumably required polymerase ribozymes capable of replicating RNA. Known polymerase ribozymes best approximating such replicases use as their catalytic engine an RNA-ligase ribozyme originally selected from random RNA sequences. Here we report 3.15-A crystal structures of this ligase trapped in catalytically viable preligation states, with the 3'-hydroxyl nucleophile positioned for in-line attack on the 5'-triphosphate. Guided by metal- and solvent-mediated interactions, the 5'-triphosphate hooks into the major groove of the adjoining RNA duplex in an unanticipated conformation. Two phosphates and the nucleophile jointly coordinate an active-site metal ion. Atomic mutagenesis experiments demonstrate that active-site nucleobase and hydroxyl groups also participate directly in catalysis, collectively playing a role that in proteinaceous polymerases is performed by a second metal ion. Thus artificial ribozymes can use complex catalytic strategies that differ markedly from those of analogous biological enzymes.
The structural basis of RNA-catalyzed RNA polymerization., Shechner DM, Bartel DP, Nat Struct Mol Biol. 2011 Aug 21;18(9):1036-42. doi: 10.1038/nsmb.2107. PMID:21857665
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.