View source for 4bxw


==Crystal Structure of the Prothrombinase Complex from the Venom of Pseudonaja Textilis==
<StructureSection load='4bxw' size='340' side='right'caption='[[4bxw]], [[Resolution|resolution]] 2.71&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bxw]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Pseudonaja_textilis Pseudonaja textilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BXW 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]] 2.71&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0GJ:L-ALPHA-GLUTAMYL-N-{(1S)-4-{[AMINO(IMINIO)METHYL]AMINO}-1-[(1S)-2-CHLORO-1-HYDROXYETHYL]BUTYL}GLYCINAMIDE'>0GJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4bxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxw OCA], [https://pdbe.org/4bxw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bxw RCSB], [https://www.ebi.ac.uk/pdbsum/4bxw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bxw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FAXC_PSETE FAXC_PSETE] Snake prothrombin activator that attacks the hemostatic system of prey. This non-catalytic subunit is functionally similar to blood coagulation factor V (PubMed:12362232, PubMed:23869089). It serves as a critical cofactor for the prothrombinase activity of the catalytic subunit, which is similar to the blood coagulation factor X (PubMed:12362232, PubMed:23869089). The complex converts prothrombin to thrombin by sequential cleavage at two positions, Arg-320 followed by Arg-271 (PubMed:23869089). Cleavage at Arg-320 produces an active intermediate known as meizothrombin (PubMed:23869089). Meizothrombin is the 'second' substrate for prothrombinase, and it docks in an altered manner to present the second cleavage site (271) (PubMed:23869089). Cleavage at Arg-271 releases active thrombin from its pro-fragment (PubMed:23869089). This order of events is reversed if the protease component of prothrombinase is used on its own, suggesting that the 271 site is inherently more accessible to proteolysis (PubMed:23869089). The complex converts prothrombin to thrombin in presence but also in the absence of membrane (PubMed:23869089).<ref>PMID:12362232</ref> <ref>PMID:23869089</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The prothrombinase complex, composed of the protease factor (f)Xa and cofactor fVa, efficiently converts prothrombin to thrombin by specific, sequential cleavage at two sites. How the complex assembles and its mechanism of prothrombin processing is of central importance to human health and disease, since insufficient thrombin generation is the root-cause of hemophilia and excessive thrombin production results in thrombosis. Efforts to determine the crystal structure of the prothrombinase complex have been thwarted by the dependence of complex formation on phospholipid membrane association. Pseutarin C is an intrinsically stable prothrombinase complex preassembled in the venom gland of the Australian Eastern Brown Snake (Pseudonaja textilis). Here we report the crystal structures of the fX-fV complex and of activated fXa from P. textilis venom, and the derived model of active Pseutarin C. Structural analysis supports a single substrate binding channel on fVa, to which prothrombin and the intermediate meizothrombin bind in two different orientations, providing insight into the architecture and mechanism of the prothrombinase complex- the molecular engine of blood coagulation.

Crystal structure of the prothrombinase complex from the venom of Pseudonaja textilis.,Lechtenberg BC, Murray-Rust TA, Johnson DJ, Adams TE, Krishnaswamy S, Camire RM, Huntington JA Blood. 2013 Jul 18. PMID:23869089<ref>PMID:23869089</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bxw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Factor Xa|Factor Xa]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Pseudonaja textilis]]
[[Category: Adams TE]]
[[Category: Camire RM]]
[[Category: Huntington JA]]
[[Category: Johnson DJD]]
[[Category: Krishnaswamy S]]
[[Category: Lechtenberg BC]]
[[Category: Murray-Rust TA]]