ArticleProceedings of the National Academy of Sciences of the United States of America2003
An oxocarbenium-ion intermediate of a ribozyme reaction indicated by kinetic isotope effects.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 36 citations in OpenAlex.
- Dissociative Transition State in Hepatitis Delta Virus Ribozyme Catalysis.Journal of the American Chemical Society · 2023Article
- Methane from microbial hydrogenolysis of sediment organic matter before the Great Oxidation Event.Nature communications · 2021Article
- Provisioning the origin and early evolution of life.Emerging topics in life sciences · 2019Article
- Prebiotic stereoselective synthesis of purine and noncanonical pyrimidine nucleotide from nucleobases and phosphorylated carbohydrates.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- DNA-catalyzed glycosylation using aryl glycoside donors.Chemical communications (Cambridge, England) · 2016Article
- Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors.Scientific reports · 2015Article
- RNA synthesis by in vitro selected ribozymes for recreating an RNA world.Life (Basel, Switzerland) · 2015Review
- Determination of relative rate constants for in vitro RNA processing reactions by internal competition.Analytical biochemistry · 2014Article
- Closing the circle: replicating RNA with RNA.Cold Spring Harbor perspectives in biology · 2010Review
- Transition states of uncatalyzed hydrolysis and aminolysis reactions of a ribosomal P-site substrate determined by kinetic isotope effects.Biochemistry · 2010Article
- Experimental analyses of the chemical dynamics of ribozyme catalysis.Current opinion in chemical biology · 2008Review
- Synthesis and analysis of substrate analogues for UDP-galactopyranose mutase: implication for an oxocarbenium ion intermediate in the catalytic mechanism.Organic letters · 2007Article
- Ribozyme motif structure mapped using random recombination and selection.RNA (New York, N.Y.) · 2005Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many of the enzymes that catalyze reactions at nucleotide glycosidic linkages proceed through either a reactive oxocarbenium-ion intermediate or a transition state with considerable oxocarbenium character. To investigate how an RNA active site deals with the catalytic challenge of nucleotide synthesis, we probed the transition state of a ribozyme able to promote the formation of a pyrimidine nucleotide. Primary and secondary kinetic isotope effects indicate that this ribozyme stabilizes a highly dissociative reaction with considerable sp2 hybridization and negligible bond order between the departing pyrophosphate leaving group and the anomeric carbon. The small primary 13C isotope effect of 1.002 +/- 0.003 indicates that the reaction is likely to be less concerted than that observed for protein nucleotide synthesis enzymes, which typically have primary 13C isotope effects of 1.02-1.03. The dissociative nature of the ribozyme reaction most resembles the reaction of some hydrolytic enzymes, such as uracil DNA glycosylase, which uses the negative charges found in the phosphodiester backbone of its DNA substrate to transiently stabilize an oxocarbenium ion during hydrolysis. The detectable hydrolysis observed in the ribozyme reaction indicates that shielding of this reactive intermediate from water is a significant challenge for RNA, which protein enzymes that synthesize nucleotides have managed to overcome during evolution, apparently by the utilization of more concerted chemistry.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.