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[[Image:2cm9.png|left|200px]]


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==The complement inhibitor OmCI in complex with ricinoleic acid==
The line below this paragraph, containing "STRUCTURE_2cm9", creates the "Structure Box" on the page.
<StructureSection load='2cm9' size='340' side='right'caption='[[2cm9]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2cm9]] is a 1 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=2CM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CM9 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=RCL:RICINOLEIC+ACID'>RCL</scene></td></tr>
{{STRUCTURE_2cm9|  PDB=2cm9  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2cm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cm9 OCA], [https://pdbe.org/2cm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cm9 RCSB], [https://www.ebi.ac.uk/pdbsum/2cm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cm9 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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cm/2cm9_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cm9 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The complement (C) system is a potent innate immune defence system against parasites. We have recently characterised and expressed OmCI, a 16 kDa protein derived from the soft tick Ornithodoros moubata that specifically binds C5, thereby preventing C activation. The structure of recombinant OmCI determined at 1.9 A resolution confirms a lipocalin fold and reveals that the protein binds a fatty acid derivative that we have identified by mass spectrometry as ricinoleic acid. We propose that OmCI could sequester one of the fatty acid-derived inflammatory modulators from the host plasma, thereby interfering with the host inflammatory response to the tick bite. Mapping of sequence differences between OmCI and other tick lipocalins with different functions, combined with biochemical investigations of OmCI activity, supports the hypothesis that OmCI acts by preventing interaction with the C5 convertase, rather than by blocking the C5a cleavage site.


===THE COMPLEMENT INHIBITOR OMCI IN COMPLEX WITH RICINOLEIC ACID===
The structure of OMCI, a novel lipocalin inhibitor of the complement system.,Roversi P, Lissina O, Johnson S, Ahmat N, Paesen GC, Ploss K, Boland W, Nunn MA, Lea SM J Mol Biol. 2007 Jun 8;369(3):784-93. Epub 2007 Mar 30. PMID:17445829<ref>PMID:17445829</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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The line below this paragraph, {{ABSTRACT_PUBMED_17445829}}, adds the Publication Abstract to the page
<div class="pdbe-citations 2cm9" style="background-color:#fffaf0;"></div>
(as it appears on PubMed at http://www.pubmed.gov), where 17445829 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_17445829}}
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
2CM9 is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Ornithodoros_moubata Ornithodoros moubata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CM9 OCA].
 
==Reference==
<ref group="xtra">PMID:17445829</ref><references group="xtra"/>
[[Category: Ornithodoros moubata]]
[[Category: Ornithodoros moubata]]
[[Category: Boland, W.]]
[[Category: Boland W]]
[[Category: Johnson, S.]]
[[Category: Johnson S]]
[[Category: Lea, S M.]]
[[Category: Lea SM]]
[[Category: Lissina, O.]]
[[Category: Lissina O]]
[[Category: Nunn, M A.]]
[[Category: Nunn MA]]
[[Category: Paesen, G C.]]
[[Category: Paesen GC]]
[[Category: Roversi, P.]]
[[Category: Roversi P]]
[[Category: C5]]
[[Category: Complement]]
[[Category: Inhibitor]]
[[Category: Lipocalin]]
[[Category: Omci]]
[[Category: Ornithodoros moubata]]
[[Category: Tick]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 22 10:46:36 2009''

Latest revision as of 17:22, 13 December 2023

The complement inhibitor OmCI in complex with ricinoleic acidThe complement inhibitor OmCI in complex with ricinoleic acid

Structural highlights

2cm9 is a 1 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 2.3Å
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The complement (C) system is a potent innate immune defence system against parasites. We have recently characterised and expressed OmCI, a 16 kDa protein derived from the soft tick Ornithodoros moubata that specifically binds C5, thereby preventing C activation. The structure of recombinant OmCI determined at 1.9 A resolution confirms a lipocalin fold and reveals that the protein binds a fatty acid derivative that we have identified by mass spectrometry as ricinoleic acid. We propose that OmCI could sequester one of the fatty acid-derived inflammatory modulators from the host plasma, thereby interfering with the host inflammatory response to the tick bite. Mapping of sequence differences between OmCI and other tick lipocalins with different functions, combined with biochemical investigations of OmCI activity, supports the hypothesis that OmCI acts by preventing interaction with the C5 convertase, rather than by blocking the C5a cleavage site.

The structure of OMCI, a novel lipocalin inhibitor of the complement system.,Roversi P, Lissina O, Johnson S, Ahmat N, Paesen GC, Ploss K, Boland W, Nunn MA, Lea SM J Mol Biol. 2007 Jun 8;369(3):784-93. Epub 2007 Mar 30. PMID:17445829[5]

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

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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

2cm9, resolution 2.30Å

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