3etb: Difference between revisions
New page: '''Unreleased structure''' The entry 3etb is ON HOLD Authors: MONZINGO, A.F., LEYSATH, C.E., BARNETT, J., IVERSON, B.L., GEORGIOU, G., ROBERTUS, J.D. Description: CRYSTAL STRUCTURE OF ... |
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The entry | ==Crystal structure of the engineered neutralizing antibody M18 complexed with anthrax protective antigen domain 4== | ||
<StructureSection load='3etb' size='340' side='right'caption='[[3etb]], [[Resolution|resolution]] 3.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3etb]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ETB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ETB 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]] 3.8Å</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=3etb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3etb OCA], [https://pdbe.org/3etb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3etb RCSB], [https://www.ebi.ac.uk/pdbsum/3etb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3etb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PAG_BACAN PAG_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax. | |||
== 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/et/3etb_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3etb ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The virulence of Bacillus anthracis is critically dependent on the cytotoxic components of the anthrax toxin, lethal factor (LF) and edema factor (EF). LF and EF gain entry into host cells through interactions with the protective antigen (PA), which binds to host cellular receptors such as CMG2. Antibodies that neutralize PA have been shown to confer protection in animal models and are undergoing intense clinical development. A murine monoclonal antibody, 14B7, has been reported to interact with domain 4 of PA (PAD4) and block its binding to CMG2. More recently, the 14B7 antibody was used as the platform for the selection of very high affinity, single-chain antibodies that have tremendous potential as a combination anthrax prophylactic and treatment. Here, we report the high-resolution X-ray structures of three high-affinity, single-chain antibodies in the 14B7 family; 14B7 and two high-affinity variants 1H and M18. In addition, we present the first neutralizing antibody-PA structure, M18 in complex with PAD4 at 3.8 A resolution. These structures provide insights into the mechanism of neutralization, and the effect of various mutations on antibody affinity, and enable a comparison between the binding of the M18 antibody and CMG2 with PAD4. | |||
Crystal structure of the engineered neutralizing antibody M18 complexed to domain 4 of the anthrax protective antigen.,Leysath CE, Monzingo AF, Maynard JA, Barnett J, Georgiou G, Iverson BL, Robertus JD J Mol Biol. 2009 Apr 3;387(3):680-93. Epub 2009 Feb 10. PMID:19361425<ref>PMID:19361425</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3etb" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bacillus anthracis]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Barnett J]] | |||
[[Category: Georgiou G]] | |||
[[Category: Iverson BL]] | |||
[[Category: Leysath CE]] | |||
[[Category: Monzingo AF]] | |||
[[Category: Robertus JD]] | |||
Latest revision as of 12:05, 30 October 2024
Crystal structure of the engineered neutralizing antibody M18 complexed with anthrax protective antigen domain 4Crystal structure of the engineered neutralizing antibody M18 complexed with anthrax protective antigen domain 4
Structural highlights
FunctionPAG_BACAN One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. PA binds to a receptor (ATR) in sensitive eukaryotic cells, thereby facilitating the translocation of the enzymatic toxin components, edema factor and lethal factor, across the target cell membrane. PA associated with LF causes death when injected, PA associated with EF produces edema. PA induces immunity to infection with anthrax. 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 PubMedThe virulence of Bacillus anthracis is critically dependent on the cytotoxic components of the anthrax toxin, lethal factor (LF) and edema factor (EF). LF and EF gain entry into host cells through interactions with the protective antigen (PA), which binds to host cellular receptors such as CMG2. Antibodies that neutralize PA have been shown to confer protection in animal models and are undergoing intense clinical development. A murine monoclonal antibody, 14B7, has been reported to interact with domain 4 of PA (PAD4) and block its binding to CMG2. More recently, the 14B7 antibody was used as the platform for the selection of very high affinity, single-chain antibodies that have tremendous potential as a combination anthrax prophylactic and treatment. Here, we report the high-resolution X-ray structures of three high-affinity, single-chain antibodies in the 14B7 family; 14B7 and two high-affinity variants 1H and M18. In addition, we present the first neutralizing antibody-PA structure, M18 in complex with PAD4 at 3.8 A resolution. These structures provide insights into the mechanism of neutralization, and the effect of various mutations on antibody affinity, and enable a comparison between the binding of the M18 antibody and CMG2 with PAD4. Crystal structure of the engineered neutralizing antibody M18 complexed to domain 4 of the anthrax protective antigen.,Leysath CE, Monzingo AF, Maynard JA, Barnett J, Georgiou G, Iverson BL, Robertus JD J Mol Biol. 2009 Apr 3;387(3):680-93. Epub 2009 Feb 10. PMID:19361425[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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