6z8w
From Proteopedia
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| - | ==== | + | ==X-ray structure of the complex between human alpha thrombin and a thrombin binding aptamer variant (TBA-3G), which contains 1-beta-D-glucopyranosyl residue in the side chain of Thy3 at N3.== |
| - | <StructureSection load='6z8w' size='340' side='right'caption='[[6z8w]]' scene=''> | + | <StructureSection load='6z8w' size='340' side='right'caption='[[6z8w]], [[Resolution|resolution]] 1.73Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6z8w]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=6Z8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z8W FirstGlance]. <br> |
| - | </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=6z8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z8w OCA], [https://pdbe.org/6z8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z8w RCSB], [https://www.ebi.ac.uk/pdbsum/6z8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z8w ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.73Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QCK:[(2~{R},3~{S},5~{R})-5-[5-methyl-2,4-bis(oxidanylidene)-3-(1~{H}-1,2,3-triazol-5-ylmethyl)pyrimidin-1-yl]-3-oxidanyl-oxolan-2-yl]methyl+dihydrogen+phosphate'>QCK</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=6z8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z8w OCA], [https://pdbe.org/6z8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z8w RCSB], [https://www.ebi.ac.uk/pdbsum/6z8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z8w ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Post-SELEX modification of DNA aptamers is an established strategy to improve their affinity or inhibitory characteristics. In this study, we examined the possibility of increasing the recognition interface between the thrombin-binding aptamer HD1 (TBA) and thrombin by adding a chemically modified side chain to selected nucleotide residues. A panel of 22 TBA variants with N3-modified residues T3 and T12 was prepared by a two-step modification procedure. Aptamers were characterized by a combination of biophysical and biochemical methods. We identified mutants with enhanced affinity and improved anticoagulant activity. The crystal structures of thrombin complexes with three selected modified variants revealed that the modified pyrimidine base invariably allocates in proximity to thrombin residues Tyr76 and Ile82 due to the directing role of the unmodified TT loop. The modifications induced an increase in the contact areas between thrombin and the modified TBAs. Comparative analysis of the structural, biochemical, and biophysical data suggests that the non-equivalent binding modes of the mutants with thrombin in the T3- and T12-modified series account for the observed systematic differences in their affinity characteristics. In this study, we show that extending the recognition surface between the protein and modified aptamers is a promising approach that may improve characteristics of aptamer ligands. | ||
| + | |||
| + | Expanding the recognition interface of the thrombin-binding aptamer HD1 through modification of residues T3 and T12.,Smirnov I, Kolganova N, Troisi R, Sica F, Timofeev E Mol Ther Nucleic Acids. 2021 Jan 16;23:863-871. doi: 10.1016/j.omtn.2021.01.004. , eCollection 2021 Mar 5. PMID:33614235<ref>PMID:33614235</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6z8w" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Thrombin 3D Structures|Thrombin 3D Structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Synthetic construct]] |
| + | [[Category: Sica F]] | ||
| + | [[Category: Timofeev EN]] | ||
| + | [[Category: Troisi R]] | ||
Current revision
X-ray structure of the complex between human alpha thrombin and a thrombin binding aptamer variant (TBA-3G), which contains 1-beta-D-glucopyranosyl residue in the side chain of Thy3 at N3.
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