View source for 8tqs


==Complex of human thrombin (S195A) bound to a bivalent inhibitor comprised of DNA Aptamer HD22 conjugated to Dabigatran with a linker.==
<StructureSection load='8tqs' size='340' side='right'caption='[[8tqs]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8tqs]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TQS 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]] 2.207&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4CC:N-[(2-{[(4-CARBAMIMIDOYLPHENYL)AMINO]METHYL}-1-METHYL-1H-BENZIMIDAZOL-5-YL)CARBONYL]-N-PYRIDIN-2-YL-BETA-ALANINE'>4CC</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8tqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tqs OCA], [https://pdbe.org/8tqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tqs RCSB], [https://www.ebi.ac.uk/pdbsum/8tqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tqs ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Potent and selective inhibition of the structurally homologous proteases of coagulation poses challenges for drug development. Hematophagous organisms frequently accomplish this by fashioning peptide inhibitors combining exosite and active site binding motifs. Inspired by this biological strategy, we create several EXACT inhibitors targeting thrombin and factor Xa de novo by linking EXosite-binding aptamers with small molecule ACTive site inhibitors. The aptamer component within the EXACT inhibitor (1) synergizes with and enhances the potency of small-molecule active site inhibitors by many hundred-fold (2) can redirect an active site inhibitor's selectivity towards a different protease, and (3) enable efficient reversal of inhibition by an antidote that disrupts bivalent binding. One EXACT inhibitor, HD22-7A-DAB, demonstrates extraordinary anticoagulation activity, exhibiting great potential as a potent, rapid onset anticoagulant to support cardiovascular surgeries. Using this generalizable molecular engineering strategy, selective, potent, and rapidly reversible EXACT inhibitors can be created against many enzymes through simple oligonucleotide conjugation for numerous research and therapeutic applications.

Aptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors.,Yu H, Kumar S, Frederiksen JW, Kolyadko VN, Pitoc G, Layzer J, Yan A, Rempel R, Francis S, Krishnaswamy S, Sullenger BA Nat Commun. 2024 May 10;15(1):3977. doi: 10.1038/s41467-024-48211-6. PMID:38730234<ref>PMID:38730234</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8tqs" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Krishnaswamy S]]
[[Category: Kumar S]]