View source for 3zuo


==OMCI in complex with leukotriene B4==
<StructureSection load='3zuo' size='340' side='right'caption='[[3zuo]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zuo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ornithodoros_moubata Ornithodoros moubata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZUO 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]] 1.86&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LTB:LEUKOTRIENE+B4'>LTB</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=3zuo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zuo OCA], [https://pdbe.org/3zuo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zuo RCSB], [https://www.ebi.ac.uk/pdbsum/3zuo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zuo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C5I_ORNMO C5I_ORNMO] Bifunctional protein derived from blood-feeding ticks that specifically prevents complement-mediated C5 activation and acts as a scavenger for inflammatory modulators such as leukotriene B4 (LTB4). C5 and LTB4 binding activities are independent (PubMed:23625922). Inhibits classical and alternative pathways of complement activation by preventing the cleavage of complement C5 by both classical and alternative C5 convertases (Probable) (PubMed:15699138). Inhibits complement in all species tested (rabbit, rat, guinea pig, mouse, pig, and human) (PubMed:27018802). Also binds fatty acids such as palmitoleic acid and ricinoleic acid, as well as inflammatory modulators LTB4 (and presumably arachidonic acid (AA)) that may be sequestered to interfere with the host inflammatory response (PubMed:23625922). Does not bind to leukotriene C4 and thromboxane B2 (PubMed:23625922). In vivo, when tested on the mouse model of immune complex-induced acute lung injury (IC-ALI), shows a potent inhibitory activity of the pathology, equally dependent on both C5 inhibition and LTB4 binding for full activity (PubMed:23625922).<ref>PMID:15699138</ref> <ref>PMID:23625922</ref> <ref>PMID:27018802</ref> <ref>PMID:17445829</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Molecules that simultaneously inhibit independent or co-dependent proinflammatory pathways may have advantages over conventional monotherapeutics. OmCI is a bifunctional protein derived from blood-feeding ticks that specifically prevents complement (C) mediated C5 activation and also sequesters leukotriene B4 (LTB4) within an internal binding pocket. Here, we examine the effect of LTB4 binding on OmCI's structure and function and investigate the relative importance of C-mediated C5 activation and LTB4 in a mouse model of immune complex-induced acute lung injury (IC-ALI). We describe two crystal structures of bacterially expressed OmCI: one binding a C16 fatty-acid and the other LTB4 (C20). We show that the molecules C5 and LTB4-binding activities are independent of each other, and that OmCI is a potent inhibitor of experimental IC-ALI, equally dependent on both C5 inhibition and LTB4 binding for full activity. The data highlight the importance of LTB4 in IC-ALI and activation of C5 by the complement pathway C5 convertase rather than by non-C proteases. The findings suggest that dual inhibition of C5 and LTB4 may be useful for treatment of human immune-complex-dependent diseases.

Bifunctional Lipocalin Ameliorates Murine Immune Complex-Induced Acute Lung Injury.,Roversi P, Ryffel B, Togbe D, Maillet I, Teixeira M, Ahmat N, Paesen GC, Lissina O, Boland W, Ploss K, Caesar JJ, Leonhartsberger S, Lea SM, Nunn MA J Biol Chem. 2013 Apr 26. PMID:23625922<ref>PMID:23625922</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zuo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Ornithodoros moubata]]
[[Category: Ahmat N]]
[[Category: Boland W]]
[[Category: Caesar JJE]]
[[Category: Couillin I]]
[[Category: Lea SM]]
[[Category: Leonhartsberger S]]
[[Category: Lissina O]]
[[Category: Maillet I]]
[[Category: Nunn MA]]
[[Category: Ploss K]]
[[Category: Quesniaux VFJ]]
[[Category: Roversi P]]
[[Category: Ryffel B]]
[[Category: Teixeira M]]
[[Category: Togbe D]]