View source for 3nht


==Crystal structure of the AnSt-D7L1-U46619 complex==
<StructureSection load='3nht' size='340' side='right'caption='[[3nht]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3nht]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Anopheles_stephensi Anopheles stephensi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NHT 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]] 1.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=U46:(5E)-7-{6-[(1E)-3-HYDROXYOCT-1-ENYL]-2-OXABICYCLO[2.2.1]HEPT-5-YL}HEPT-5-ENOIC+ACID'>U46</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=3nht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nht OCA], [https://pdbe.org/3nht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nht RCSB], [https://www.ebi.ac.uk/pdbsum/3nht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nht ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D7L1_ANOST D7L1_ANOST] Modulates blood feeding of female mosquitoes on vertebrate species by binding and sequestering different mediators involved in the host response (By similarity). Binds leukotriene C4, leukotriene D4, leukotriene E4 and stable analogs of thromboxane A2, U-46619 and carbocyclic TXA2 (PubMed:21152418). Binds weakly prostaglandins: PGD2, PGE2 and PGF2alpha (PubMed:21152418). Does not bind leukotriene B4, biogenic amines, ADP, platelet activating phospholipid derivative PAF and arachidonic acid (PubMed:21152418). Inhibits agonist-induced smooth muscle contraction (PubMed:21152418). Inhibits platelet aggregation induced by low concentrations of collagen in thromboxane A2-dependent manner (PubMed:21152418).[UniProtKB:P18153]<ref>PMID:21152418</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The highly expressed D7 protein family of mosquito saliva has previously been shown to act as an anti-inflammatory mediator by binding host biogenic amines and cysteinyl leukotrienes (CysLTs). In this study we demonstrate that AnSt-D7L1, a two-domain member of this group from Anopheles stephensi, retains the CysLT binding function seen in the homolog AeD7 from Aedes aegypti but has lost the ability to bind biogenic amines. Unlike any previously characterized members of the D7 family, AnSt-D7L1 has acquired the important function of binding thromboxane A(2) (TXA(2)) and its analogs with high affinity. When administered to tissue preparations, AnSt-D7L1 abrogated Leukotriene C(4) (LTC(4))-induced contraction of guinea pig ileum and contraction of rat aorta by the TXA(2) analog U46619. The protein also inhibited platelet aggregation induced by both collagen and U46619 when administered to stirred platelets. The crystal structure of AnSt-D7L1 contains two OBP-like domains and has a structure similar to AeD7. In AnSt-D7L1, the binding pocket of the C-terminal domain has been rearranged relative to AeD7, making the protein unable to bind biogenic amines. Structures of the ligand complexes show that CysLTs and TXA(2) analogs both bind in the same hydrophobic pocket of the N-terminal domain. The TXA(2) analog U46619 is stabilized by hydrogen bonding interactions of the omega-5 hydroxyl group with the phenolic hydroxyl group of Tyr 52. LTC(4) and occupies a very similar position to LTE(4) in the previously determined structure of its complex with AeD7. As yet, it is not known what, if any, new function has been acquired by the rearranged C-terminal domain. This article presents, to our knowledge, the first structural characterization of a protein from mosquito saliva that inhibits collagen mediated platelet activation.

The function and three-dimensional structure of a thromboxane A2/cysteinyl leukotriene-binding protein from the saliva of a mosquito vector of the malaria parasite.,Alvarenga PH, Francischetti IM, Calvo E, Sa-Nunes A, Ribeiro JM, Andersen JF PLoS Biol. 2010 Nov 30;8(11):e1000547. PMID:21152418<ref>PMID:21152418</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3nht" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Anopheles stephensi]]
[[Category: Large Structures]]
[[Category: Alvarenga PH]]
[[Category: Andersen JF]]
[[Category: Calvo E]]
[[Category: Francischetti IM]]
[[Category: Ribeiro JM]]
[[Category: Sa-Nunes A]]