7ntu: Difference between revisions

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<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>
<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>
== Disease ==
[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[https://omim.org/entry/613679 613679]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref>  Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref>  Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[https://omim.org/entry/188050 188050]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis.  Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[https://omim.org/entry/614390 614390]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
== Function ==
[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==

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

7ntu is a 8 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.1Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Troisi R, Balasco N, Santamaria A, Vitagliano L, Sica F. Structural and functional analysis of the simultaneous binding of two duplex/quadruplex aptamers to human α-thrombin. Int J Biol Macromol. 2021 Jun 30;181:858-867. PMID:33864869 doi:10.1016/j.ijbiomac.2021.04.076

7ntu, resolution 3.10Å

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