View source for 7mj5


==complex of human thrombin with XC-43==
<StructureSection load='7mj5' size='340' side='right'caption='[[7mj5]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7mj5]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopsylla_cheopis Xenopsylla cheopis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MJ5 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]] 2.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7mj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mj5 OCA], [https://pdbe.org/7mj5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mj5 RCSB], [https://www.ebi.ac.uk/pdbsum/7mj5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mj5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A2IAB2_9NEOP A2IAB2_9NEOP] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The salivary glands of the flea Xenopsylla cheopis, a vector of the plague bacterium, Yersinia pestis, express proteins and peptides thought to target the hemostatic and inflammatory systems of its mammalian hosts. Past transcriptomic analyses of salivary gland tissue revealed the presence of two similar peptides (XC-42 and XC-43) having no extensive similarities to any other deposited sequences. Here we show that these peptides specifically inhibit coagulation of plasma and the amidolytic activity of alpha-thrombin. XC-43, the smaller of the two peptides, is a fast, tight-binding inhibitor of thrombin with a dissociation constant of less than 10 pM. XC-42 exhibits similar selectivity as well as kinetic and binding properties. The crystal structure of XC-43 in complex with thrombin shows that despite its substrate-like binding mode, XC-43 is not detectably cleaved by thrombin and that it interacts with the thrombin surface from the enzyme catalytic site through the fibrinogen-binding exosite I. The low rate of hydrolysis was verified in solution experiments with XC-43, which show the substrate to be largely intact after 2 h of incubation with thrombin at 37 degrees C. The low rate of XC-43 cleavage by thrombin may be attributable to specific changes in the catalytic triad observable in the crystal structure of the complex or to extensive interactions in the prime sites that may stabilize the binding of cleavage products. Based on the increased arterial occlusion time, tail bleeding time, and blood coagulation parameters in rat models of thrombosis XC-43 could be valuable as an anticoagulant.

Identification of a substrate-like cleavage-resistant thrombin inhibitor from the saliva of the flea Xenopsylla cheopis.,Lu S, Tirloni L, Oliveira MB, Bosio CF, Nardone GA, Zhang Y, Hinnebusch BJ, Ribeiro JM, Andersen JF J Biol Chem. 2021 Nov;297(5):101322. doi: 10.1016/j.jbc.2021.101322. Epub 2021 , Oct 21. PMID:34688666<ref>PMID:34688666</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7mj5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thrombin 3D Structures|Thrombin 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Xenopsylla cheopis]]
[[Category: Andersen JF]]
[[Category: Lu S]]
[[Category: Tirloni L]]