8tdy: Difference between revisions
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==16mer self-complementary duplex RNA with D:U pair sequence 1== | |||
<StructureSection load='8tdy' size='340' side='right'caption='[[8tdy]], [[Resolution|resolution]] 1.66Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8tdy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TDY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TDY FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.66Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=N6G:((2R,3S,4R,5S)-5-(2,6-DIAMINO-9H-PURIN-9-YL)-3,4-DIHYDROXY-TETRAHYDROFURAN-2-YL)METHYL+DIHYDROGEN+PHOSPHATE'>N6G</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8tdy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tdy OCA], [https://pdbe.org/8tdy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tdy RCSB], [https://www.ebi.ac.uk/pdbsum/8tdy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tdy ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In the RNA World before the emergence of an RNA polymerase, nonenzymatic template copying would have been essential for the transmission of genetic information. However, the products of chemical copying with the canonical nucleotides (A, U, C, and G) are heavily biased toward the incorporation of G and C, which form a more stable base pair than A and U. We therefore asked whether replacing adenine (A) with diaminopurine (D) might lead to more efficient and less biased nonenzymatic template copying by making a stronger version of the A:U pair. As expected, primer extension substrates containing D bound to U in the template more tightly than substrates containing A. However, primer extension with D exhibited elevated reaction rates on a C template, leading to concerns about fidelity. Our crystallographic studies revealed the nature of the D:C mismatch by showing that D can form a wobble-type base pair with C. We then asked whether competition with G would decrease the mismatched primer extension. We performed nonenzymatic primer extension with all four activated nucleotides on randomized RNA templates containing all four letters and used deep sequencing to analyze the products. We found that the DUCG genetic system exhibited a more even product distribution and a lower mismatch frequency than the canonical AUCG system. Furthermore, primer extension is greatly reduced following all mismatches, including the D:C mismatch. Our study suggests that D deserves further attention for its possible role in the RNA World and as a potentially useful component of artificial nonenzymatic RNA replication systems. | |||
Diaminopurine in Nonenzymatic RNA Template Copying.,Jia X, Fang Z, Kim SC, Ding D, Zhou L, Szostak JW J Am Chem Soc. 2024 May 31. doi: 10.1021/jacs.4c02560. PMID:38818863<ref>PMID:38818863</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Fang | <div class="pdbe-citations 8tdy" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Fang Z]] | |||
[[Category: Jia X]] | |||
[[Category: Szostak JW]] | |||
Latest revision as of 08:03, 12 June 2024
16mer self-complementary duplex RNA with D:U pair sequence 116mer self-complementary duplex RNA with D:U pair sequence 1
Structural highlights
Publication Abstract from PubMedIn the RNA World before the emergence of an RNA polymerase, nonenzymatic template copying would have been essential for the transmission of genetic information. However, the products of chemical copying with the canonical nucleotides (A, U, C, and G) are heavily biased toward the incorporation of G and C, which form a more stable base pair than A and U. We therefore asked whether replacing adenine (A) with diaminopurine (D) might lead to more efficient and less biased nonenzymatic template copying by making a stronger version of the A:U pair. As expected, primer extension substrates containing D bound to U in the template more tightly than substrates containing A. However, primer extension with D exhibited elevated reaction rates on a C template, leading to concerns about fidelity. Our crystallographic studies revealed the nature of the D:C mismatch by showing that D can form a wobble-type base pair with C. We then asked whether competition with G would decrease the mismatched primer extension. We performed nonenzymatic primer extension with all four activated nucleotides on randomized RNA templates containing all four letters and used deep sequencing to analyze the products. We found that the DUCG genetic system exhibited a more even product distribution and a lower mismatch frequency than the canonical AUCG system. Furthermore, primer extension is greatly reduced following all mismatches, including the D:C mismatch. Our study suggests that D deserves further attention for its possible role in the RNA World and as a potentially useful component of artificial nonenzymatic RNA replication systems. Diaminopurine in Nonenzymatic RNA Template Copying.,Jia X, Fang Z, Kim SC, Ding D, Zhou L, Szostak JW J Am Chem Soc. 2024 May 31. doi: 10.1021/jacs.4c02560. PMID:38818863[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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