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      Differential Assembly of Catalytic Interactions within the Conserved Active Sites of Two Ribozymes

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          Abstract

          Molecular recognition is central to biology and a critical aspect of RNA function. Yet structured RNAs typically lack the preorganization needed for strong binding and precise positioning. A striking example is the group I ribozyme from Tetrahymena, which binds its guanosine substrate (G) orders of magnitude slower than diffusion. Binding of G is also thermodynamically coupled to binding of the oligonucleotide substrate (S) and further work has shown that the transition from E•G to E•S•G accompanies a conformational change that allows G to make the active site interactions required for catalysis. The group I ribozyme from Azoarcus has a similarly slow association rate but lacks the coupled binding observed for the Tetrahymena ribozyme. Here we test, using G analogs and metal ion rescue experiments, whether this absence of coupling arises from a higher degree of preorganization within the Azoarcus active site. Our results suggest that the Azoarcus ribozyme forms cognate catalytic metal ion interactions with G in the E•G complex, interactions that are absent in the Tetrahymena E•G complex. Thus, RNAs that share highly similar active site architectures and catalyze the same reactions can differ in the assembly of transition state interactions. More generally, an ability to readily access distinct local conformational states may have facilitated the evolutionary exploration needed to attain RNA machines that carry out complex, multi-step processes.

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          Most cited references 43

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          RNA chaperones and the RNA folding problem.

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            Mechanical Devices of the Spliceosome: Motors, Clocks, Springs, and Things

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              Structural basis of the translational elongation cycle.

              The sequential addition of amino acids to a growing polypeptide chain is carried out by the ribosome in a complicated multistep process called the elongation cycle. It involves accurate selection of each aminoacyl tRNA as dictated by the mRNA codon, catalysis of peptide bond formation, and movement of the tRNAs and mRNA through the ribosome. The process requires the GTPase factors elongation factor Tu (EF-Tu) and EF-G. Not surprisingly, large conformational changes in both the ribosome and its tRNA substrates occur throughout protein elongation. Major advances in our understanding of the elongation cycle have been made in the past few years as a result of high-resolution crystal structures that capture various states of the process, as well as biochemical and computational studies.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 August 2016
                2016
                : 11
                : 8
                Affiliations
                [1 ]Department of Biochemistry, Stanford University, Stanford, California, 94305, United States of America
                [2 ]Leiden Institute of Chemistry, Leiden University, Leiden, 2333 CC, the Netherlands
                [3 ]Departments of Chemical Engineering and Chemistry, Stanford University, Stanford, California, 94305, United States of America
                [4 ]Stanford ChEM-H (Chemistry, Engineering, and Medicine for Human Health), Stanford University, Stanford, California, 94305, United States of America
                Oak Ridge National Laboratory, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceived and designed the experiments: SNS RNS DH.

                • Performed the experiments: SNS RNS.

                • Analyzed the data: SNS RNS.

                • Wrote the paper: SNS RNS DH.

                Article
                PONE-D-16-16517
                10.1371/journal.pone.0160457
                4976970
                27501145
                © 2016 van Schie et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 3, Tables: 0, Pages: 16
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: GM049243
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 5 T32 GM007276
                Award Recipient :
                This work was supported by National Institutes of Health grant GM049243 ( https://www.nih.gov/) to DH, and National Institutes of Health Training Grant 5 T32 GM007276 ( https://www.nih.gov/) to RNS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzymes
                Ribozymes
                Biology and Life Sciences
                Biochemistry
                Proteins
                Enzymes
                Ribozymes
                Biology and Life Sciences
                Biochemistry
                Nucleic Acids
                RNA
                Ribozymes
                Biology and Life Sciences
                Organisms
                Protozoans
                Ciliate Protozoans
                Tetrahymena
                Physical Sciences
                Chemistry
                Physical Chemistry
                Reaction Dynamics
                Transition State
                Physical Sciences
                Chemistry
                Physical Chemistry
                Chemical Equilibrium
                Physical Sciences
                Physics
                Thermodynamics
                Biology and Life Sciences
                Computational Biology
                Genome Complexity
                Introns
                Biology and Life Sciences
                Genetics
                Genomics
                Genome Complexity
                Introns
                Biology and life sciences
                Molecular biology
                Macromolecular structure analysis
                RNA structure
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                RNA structure
                Physical Sciences
                Chemistry
                Catalysis
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized

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