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2vxv

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Crystal structure of human IgG ABT-325 Fab Fragment

Structural highlights

2vxv is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.49Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 unique cytokine interleukin-18 (IL-18) acts synergistically with IL-12 to regulate T-helper 1 and 2 lymphocytes and, as such, seems to underlie the pathogenesis of various autoimmune and allergic diseases. Several anti-IL-18 agents are in clinical development, including the recombinant human antibody ABT-325, which is entering trials for autoimmune diseases. Given competing cytokine/receptor and cytokine/receptor decoy interactions, understanding the structural basis for recognition is critical for effective development of anti-cytokine therapies. Here we report three crystal structures: the murine antibody 125-2H Fab fragment bound to human IL-18, at 1.5 A resolution; the 125-2H Fab (2.3 A); and the ABT-325 Fab (1.5 A). These structures, along with human/mouse IL-18 chimera binding data, allow us to make three key observations relevant to the biology and antigenic recognition of IL-18 and related cytokines. First, several IL-18 residues shift dramatically (> 10 A) upon binding 125-2H, compared with unbound IL-18 (Kato, Z., Jee, J., Shikano, H., Mishima, M., Ohki, I., Ohnishi, H., Li, A., Hashimoto, K., Matsukuma, E., Omoya, K., Yamamoto, Y., Yoneda, T., Hara, T., Kondo, N., and Shirakawa, M. (2003) Nat. Struct. Biol. 10, 966-971). IL-18 thus exhibits plasticity that may be common to its interactions with other receptors. Related cytokines may exhibit similar plasticity. Second, ABT-325 and 125-2H differ significantly in combining site character and architecture, thus explaining their ability to bind IL-18 simultaneously at distinct epitopes. These data allow us to define the likely ABT-325 epitope and thereby explain the distinct neutralizing mechanisms of both antibodies. Third, given the high 125-2H potency, 10 well ordered water molecules are trapped upon complex formation in a cavity between two IL-18 loops and all six 125-2H complementarity-determining regions. Thus, counterintuitively, tight and specific antibody binding may in some cases be water-mediated.

Unusual water-mediated antigenic recognition of the proinflammatory cytokine interleukin-18.,Argiriadi MA, Xiang T, Wu C, Ghayur T, Borhani DW J Biol Chem. 2009 Sep 4;284(36):24478-89. Epub 2009 Jun 24. PMID:19553661^[1]

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

References

↑ Argiriadi MA, Xiang T, Wu C, Ghayur T, Borhani DW. Unusual water-mediated antigenic recognition of the proinflammatory cytokine interleukin-18. J Biol Chem. 2009 Sep 4;284(36):24478-89. Epub 2009 Jun 24. PMID:19553661 doi:10.1074/jbc.M109.023887

1 Structural highlights
2 Evolutionary Conservation
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/2vxv"

@@ Line 3: / Line 3: @@
 <StructureSection load='2vxv' size='340' side='right'caption='[[2vxv]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2vxv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VXV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VXV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2vxv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VXV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CXS:3-CYCLOHEXYL-1-PROPYLSULFONIC+ACID'>CXS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.49&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vxu|2vxu]], [[2vxt|2vxt]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CXS:3-CYCLOHEXYL-1-PROPYLSULFONIC+ACID'>CXS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vxv OCA], [http://pdbe.org/2vxv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vxv RCSB], [http://www.ebi.ac.uk/pdbsum/2vxv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vxv ProSAT]</span></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=2vxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vxv OCA], [https://pdbe.org/2vxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vxv RCSB], [https://www.ebi.ac.uk/pdbsum/2vxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vxv ProSAT]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 13: / Line 13: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vx/2vxv_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 31: / Line 31: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Argiriadi, M A]]
+[[Category: Argiriadi MA]]
-[[Category: Borhani, D W]]
+[[Category: Borhani DW]]
-[[Category: Ghayur, T]]
+[[Category: Ghayur T]]
-[[Category: Wu, C]]
+[[Category: Wu C]]
-[[Category: Xiang, T]]
+[[Category: Xiang T]]
-[[Category: Autoimmunity]]
-[[Category: Fab]]
-[[Category: Il-18]]
-[[Category: Immune system]]
-[[Category: Th1/th2 cell]]

2vxv

From Proteopedia

Current revision

Crystal structure of human IgG ABT-325 Fab Fragment

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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