8sv3: Difference between revisions
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==7-Deazapurines and 5-Halogenpyrimidine DNA duplex== | |||
<StructureSection load='8sv3' size='340' side='right'caption='[[8sv3]], [[Resolution|resolution]] 1.51Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8sv3]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Alkalihalobacillus_halodurans Alkalihalobacillus halodurans] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SV3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SV3 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]] 1.51Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7DA:7-DEAZA-2-DEOXYADENOSINE-5-MONOPHOSPHATE'>7DA</scene>, <scene name='pdbligand=7GU:7-DEAZA-2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>7GU</scene>, <scene name='pdbligand=B86:2-DEOXY-5-FLUOROCYTIDINE'>B86</scene>, <scene name='pdbligand=C37:5-FLUORO-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>C37</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=UCL:5-CHLORO-2-DEOXYURIDINE+5-(DIHYDROGEN+PHOSPHATE)'>UCL</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=8sv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sv3 OCA], [https://pdbe.org/8sv3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sv3 RCSB], [https://www.ebi.ac.uk/pdbsum/8sv3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sv3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RNH1_HALH5 RNH1_HALH5] Endonuclease that specifically degrades the RNA of RNA-DNA hybrids.<ref>PMID:15989951</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Several efforts are currently directed at the creation and cellular implementation of alternative genetic systems composed of pairing components that are orthogonal to the natural dA/dT and dG/dC base pairs. In an alternative approach, Watson-Crick-type pairing is conserved, but one or all of the four letters of the A, C, G, and T alphabet are substituted by modified components. Thus, all four nucleobases were altered to create halogenated deazanucleic acid (DZA): dA was replaced by 7-deaza-2'-deoxyadenosine (dzA), dG by 7-deaza-2'-deoxyguanosine (dzG), dC by 5-fluoro-2'-deoxycytidine (FdC), and dT by 5-chloro-2'-deoxyuridine (CldU). This base-pairing system was previously shown to retain function in Escherichia coli. Here, we analyze the stability, hydration, structure, and dynamics of a DZA Dickerson-Drew Dodecamer (DDD) of sequence 5'-FdC-dzG-FdC-dzG-dzA-dzA-CldU-CldU-FdC-dzG-FdC-dzG-3'. Contrary to similar stabilities of DDD and DZA-DDD, osmotic stressing revealed a dramatic loss of hydration for the DZA-DDD relative to that for the DDD. The parent DDD 5'-d(CGCGAATTCGCG)-3' features an A-tract, a run of adenosines uninterrupted by a TpA step, and exhibits a hallmark narrow minor groove. Crystal structures horizontal line in the presence of RNase H horizontal line and MD simulations show increased conformational plasticity ("morphing") of DZA-DDD relative to that of the DDD. The narrow dzA-tract minor groove in one structure widens to resemble that in canonical B-DNA in a second structure. These changes reflect an indirect consequence of altered DZA major groove electrostatics (less negatively polarized compared to that in DNA) and hydration (reduced compared to that in DNA). Therefore, chemical modifications outside the minor groove that lead to collapse of major groove electrostatics and hydration can modulate A-tract geometry. | |||
Conformational Morphing by a DNA Analogue Featuring 7-Deazapurines and 5-Halogenpyrimidines and the Origins of Adenine-Tract Geometry.,Pallan PS, Lybrand TP, Rozners E, Abramov M, Schepers G, Eremeeva E, Herdewijn P, Egli M Biochemistry. 2023 Oct 3;62(19):2854-2867. doi: 10.1021/acs.biochem.3c00327. Epub , 2023 Sep 11. PMID:37694722<ref>PMID:37694722</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8sv3" style="background-color:#fffaf0;"></div> | ||
[[Category: Egli | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Alkalihalobacillus halodurans]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Egli M]] | |||
[[Category: Pallan PS]] | |||
Latest revision as of 15:36, 4 October 2023
7-Deazapurines and 5-Halogenpyrimidine DNA duplex7-Deazapurines and 5-Halogenpyrimidine DNA duplex
Structural highlights
FunctionRNH1_HALH5 Endonuclease that specifically degrades the RNA of RNA-DNA hybrids.[1] Publication Abstract from PubMedSeveral efforts are currently directed at the creation and cellular implementation of alternative genetic systems composed of pairing components that are orthogonal to the natural dA/dT and dG/dC base pairs. In an alternative approach, Watson-Crick-type pairing is conserved, but one or all of the four letters of the A, C, G, and T alphabet are substituted by modified components. Thus, all four nucleobases were altered to create halogenated deazanucleic acid (DZA): dA was replaced by 7-deaza-2'-deoxyadenosine (dzA), dG by 7-deaza-2'-deoxyguanosine (dzG), dC by 5-fluoro-2'-deoxycytidine (FdC), and dT by 5-chloro-2'-deoxyuridine (CldU). This base-pairing system was previously shown to retain function in Escherichia coli. Here, we analyze the stability, hydration, structure, and dynamics of a DZA Dickerson-Drew Dodecamer (DDD) of sequence 5'-FdC-dzG-FdC-dzG-dzA-dzA-CldU-CldU-FdC-dzG-FdC-dzG-3'. Contrary to similar stabilities of DDD and DZA-DDD, osmotic stressing revealed a dramatic loss of hydration for the DZA-DDD relative to that for the DDD. The parent DDD 5'-d(CGCGAATTCGCG)-3' features an A-tract, a run of adenosines uninterrupted by a TpA step, and exhibits a hallmark narrow minor groove. Crystal structures horizontal line in the presence of RNase H horizontal line and MD simulations show increased conformational plasticity ("morphing") of DZA-DDD relative to that of the DDD. The narrow dzA-tract minor groove in one structure widens to resemble that in canonical B-DNA in a second structure. These changes reflect an indirect consequence of altered DZA major groove electrostatics (less negatively polarized compared to that in DNA) and hydration (reduced compared to that in DNA). Therefore, chemical modifications outside the minor groove that lead to collapse of major groove electrostatics and hydration can modulate A-tract geometry. Conformational Morphing by a DNA Analogue Featuring 7-Deazapurines and 5-Halogenpyrimidines and the Origins of Adenine-Tract Geometry.,Pallan PS, Lybrand TP, Rozners E, Abramov M, Schepers G, Eremeeva E, Herdewijn P, Egli M Biochemistry. 2023 Oct 3;62(19):2854-2867. doi: 10.1021/acs.biochem.3c00327. Epub , 2023 Sep 11. PMID:37694722[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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