3zuo

From Proteopedia

(Difference between revisions)

Revision as of 11:13, 20 December 2023

OMCI in complex with leukotriene B4

Structural highlights

3zuo is a 4 chain structure with sequence from Ornithodoros moubata. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.86Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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 (PubMed:15699138) (Probable). 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).^[1] ^[2] ^[3] ^[4]

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^[5]

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

References

↑ Nunn MA, Sharma A, Paesen GC, Adamson S, Lissina O, Willis AC, Nuttall PA. Complement inhibitor of C5 activation from the soft tick Ornithodoros moubata. J Immunol. 2005 Feb 15;174(4):2084-91. PMID:15699138 doi:10.4049/jimmunol.174.4.2084
↑ 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. Bifunctional Lipocalin Ameliorates Murine Immune Complex-Induced Acute Lung Injury. J Biol Chem. 2013 Apr 26. PMID:23625922 doi:10.1074/jbc.M112.420331
↑ Jore MM, Johnson S, Sheppard D, Barber NM, Li YI, Nunn MA, Elmlund H, Lea SM. Structural basis for therapeutic inhibition of complement C5. Nat Struct Mol Biol. 2016 May;23(5):378-86. doi: 10.1038/nsmb.3196. Epub 2016 Mar, 28. PMID:27018802 doi:http://dx.doi.org/10.1038/nsmb.3196
↑ Roversi P, Lissina O, Johnson S, Ahmat N, Paesen GC, Ploss K, Boland W, Nunn MA, Lea SM. The structure of OMCI, a novel lipocalin inhibitor of the complement system. J Mol Biol. 2007 Jun 8;369(3):784-93. Epub 2007 Mar 30. PMID:17445829 doi:10.1016/j.jmb.2007.03.064
↑ 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. Bifunctional Lipocalin Ameliorates Murine Immune Complex-Induced Acute Lung Injury. J Biol Chem. 2013 Apr 26. PMID:23625922 doi:10.1074/jbc.M112.420331

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3zuo"

@@ Line 3: / Line 3: @@
 <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/Argasid_tick Argasid tick]. 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>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LTB:LEUKOTRIENE+B4'>LTB</scene></td></tr>
+</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2cm9|2cm9]], [[2cm4|2cm4]], [[3zui|3zui]]</div></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 (PubMed:15699138) (Probable). 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 ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Argasid tick]]
 [[Category: Large Structures]]
-[[Category: Ahmat, N]]
+[[Category: Ornithodoros moubata]]
-[[Category: Boland, W]]
+[[Category: Ahmat N]]
-[[Category: Caesar, J J.E]]
+[[Category: Boland W]]
-[[Category: Couillin, I]]
+[[Category: Caesar JJE]]
-[[Category: Lea, S M]]
+[[Category: Couillin I]]
-[[Category: Leonhartsberger, S]]
+[[Category: Lea SM]]
-[[Category: Lissina, O]]
+[[Category: Leonhartsberger S]]
-[[Category: Maillet, I]]
+[[Category: Lissina O]]
-[[Category: Nunn, M A]]
+[[Category: Maillet I]]
-[[Category: Ploss, K]]
+[[Category: Nunn MA]]
-[[Category: Quesniaux, V F.J]]
+[[Category: Ploss K]]
-[[Category: Roversi, P]]
+[[Category: Quesniaux VFJ]]
-[[Category: Ryffel, B]]
+[[Category: Roversi P]]
-[[Category: Teixeira, M]]
+[[Category: Ryffel B]]
-[[Category: Togbe, D]]
+[[Category: Teixeira M]]
-[[Category: Immune system]]
+[[Category: Togbe D]]

3zuo

From Proteopedia

Revision as of 11:13, 20 December 2023

OMCI in complex with leukotriene B4

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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