Show simple item record

dc.contributor.authorShechner, David M
dc.contributor.authorBartel, David
dc.contributor.authorShechner, David M.
dc.date.accessioned2014-01-08T21:33:44Z
dc.date.available2014-01-08T21:33:44Z
dc.date.issued2011-08
dc.date.submitted2011-01
dc.identifier.issn1545-9993
dc.identifier.issn1545-9985
dc.identifier.urihttp://hdl.handle.net/1721.1/83621
dc.description.abstractEarly 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.sponsorshipNational Institutes of Health (U.S.) (grant GM06183)en_US
dc.description.sponsorshipNational Center for Research Resources (U.S.) (award RR-1530)en_US
dc.description.sponsorshipUnited States. Dept. of Energy (Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH1135)en_US
dc.language.isoen_US
dc.publisherElsevier B.V.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/nsmb.2107en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourcePMCen_US
dc.titleThe structural basis of RNA-catalyzed RNA polymerizationen_US
dc.typeArticleen_US
dc.identifier.citationShechner, 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.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorBartel, Daviden_US
dc.contributor.mitauthorShechner, David M.en_US
dc.relation.journalNature Structural & Molecular Biologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsShechner, David M; Bartel, David Pen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-3872-2856
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record