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==== | ==X-ray structure of the complex between human alpha thrombin and two duplex/quadruplex aptamers: NU172 and HD22_27mer== | ||
<StructureSection load='7ntu' size='340' side='right'caption='[[7ntu]]' scene=''> | <StructureSection load='7ntu' size='340' side='right'caption='[[7ntu]], [[Resolution|resolution]] 3.10Å' 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'>[[7ntu]] is a 8 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=7NTU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NTU 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=7ntu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ntu OCA], [https://pdbe.org/7ntu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ntu RCSB], [https://www.ebi.ac.uk/pdbsum/7ntu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ntu 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]] 3.1Å</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7ntu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ntu OCA], [https://pdbe.org/7ntu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ntu RCSB], [https://www.ebi.ac.uk/pdbsum/7ntu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ntu ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The long-range communication between the two exosites of human alpha-thrombin (thrombin) tightly modulates the protein-effector interactions. Duplex/quadruplex aptamers represent an emerging class of very effective binders of thrombin. Among them, NU172 and HD22 aptamers are at the forefront of exosite I and II recognition, respectively. The present study investigates the simultaneous binding of these two aptamers by combining a structural and dynamics approach. The crystal structure of the ternary complex formed by the thrombin with NU172 and HD22_27mer provides a detailed view of the simultaneous binding of these aptamers to the protein, inspiring the design of novel bivalent thrombin inhibitors. The crystal structure represents the starting model for molecular dynamics studies, which point out the cooperation between the binding at the two exosites. In particular, the binding of an aptamer to its exosite reduces the intrinsic flexibility of the other exosite, that preferentially assumes conformations similar to those observed in the bound state, suggesting a predisposition to interact with the other aptamer. This behaviour is reflected in a significant increase of the anticoagulant activity of NU172 when the inactive HD22_27mer is bound to exosite II, providing a clear evidence of the synergic action of the two aptamers. | |||
Structural and functional analysis of the simultaneous binding of two duplex/quadruplex aptamers to human alpha-thrombin.,Troisi R, Balasco N, Santamaria A, Vitagliano L, Sica F Int J Biol Macromol. 2021 Jun 30;181:858-867. doi: , 10.1016/j.ijbiomac.2021.04.076. Epub 2021 Apr 14. PMID:33864869<ref>PMID:33864869</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7ntu" 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: Santamaria A]] | |||
[[Category: Sica F]] | |||
[[Category: Troisi R]] | |||
Latest revision as of 12:01, 17 October 2024
X-ray structure of the complex between human alpha thrombin and two duplex/quadruplex aptamers: NU172 and HD22_27merX-ray structure of the complex between human alpha thrombin and two duplex/quadruplex aptamers: NU172 and HD22_27mer
Structural highlights
Publication Abstract from PubMedThe long-range communication between the two exosites of human alpha-thrombin (thrombin) tightly modulates the protein-effector interactions. Duplex/quadruplex aptamers represent an emerging class of very effective binders of thrombin. Among them, NU172 and HD22 aptamers are at the forefront of exosite I and II recognition, respectively. The present study investigates the simultaneous binding of these two aptamers by combining a structural and dynamics approach. The crystal structure of the ternary complex formed by the thrombin with NU172 and HD22_27mer provides a detailed view of the simultaneous binding of these aptamers to the protein, inspiring the design of novel bivalent thrombin inhibitors. The crystal structure represents the starting model for molecular dynamics studies, which point out the cooperation between the binding at the two exosites. In particular, the binding of an aptamer to its exosite reduces the intrinsic flexibility of the other exosite, that preferentially assumes conformations similar to those observed in the bound state, suggesting a predisposition to interact with the other aptamer. This behaviour is reflected in a significant increase of the anticoagulant activity of NU172 when the inactive HD22_27mer is bound to exosite II, providing a clear evidence of the synergic action of the two aptamers. Structural and functional analysis of the simultaneous binding of two duplex/quadruplex aptamers to human alpha-thrombin.,Troisi R, Balasco N, Santamaria A, Vitagliano L, Sica F Int J Biol Macromol. 2021 Jun 30;181:858-867. doi: , 10.1016/j.ijbiomac.2021.04.076. Epub 2021 Apr 14. PMID:33864869[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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