dc.contributor.author | Shechner, David M | |
dc.contributor.author | Bartel, David | |
dc.contributor.author | Shechner, David M. | |
dc.date.accessioned | 2014-01-08T21:33:44Z | |
dc.date.available | 2014-01-08T21:33:44Z | |
dc.date.issued | 2011-08 | |
dc.date.submitted | 2011-01 | |
dc.identifier.issn | 1545-9993 | |
dc.identifier.issn | 1545-9985 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/83621 | |
dc.description.abstract | 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-Å 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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (grant GM06183) | en_US |
dc.description.sponsorship | National Center for Research Resources (U.S.) (award RR-1530) | en_US |
dc.description.sponsorship | United States. Dept. of Energy (Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH1135) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier B.V. | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/nsmb.2107 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike 3.0 | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/ | en_US |
dc.source | PMC | en_US |
dc.title | The structural basis of RNA-catalyzed RNA polymerization | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Shechner, David M, and David P Bartel. “The structural basis of RNA-catalyzed RNA polymerization.” Nature Structural & Molecular Biology 18, no. 9 (August 21, 2011): 1036-1042. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.mitauthor | Bartel, David | en_US |
dc.contributor.mitauthor | Shechner, David M. | en_US |
dc.relation.journal | Nature Structural & Molecular Biology | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Shechner, David M; Bartel, David P | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-3872-2856 | |
mit.license | OPEN_ACCESS_POLICY | en_US |
mit.metadata.status | Complete | |