6c5k: Difference between revisions
New page: '''Unreleased structure''' The entry 6c5k is ON HOLD Authors: Haji-Ghassemi, O., Evans, S.V. Description: S25-23 Fab in complex with Chlamydiaceae LPS (Crystal form 2) [[Category: Unre... |
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==S25-23 Fab in complex with Chlamydiaceae LPS (Crystal form 2)== | |||
<StructureSection load='6c5k' size='340' side='right'caption='[[6c5k]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6c5k]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C5K 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]] 1.75Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GP1:GLUCOSAMINE+1-PHOSPHATE'>GP1</scene>, <scene name='pdbligand=KDO:3-DEOXY-D-MANNO-OCT-2-ULOSONIC+ACID'>KDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=Z9M:2-AMINO-2-DEOXY-4-O-PHOSPHONO-BETA-D-GLUCOPYRANOSE'>Z9M</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=6c5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c5k OCA], [https://pdbe.org/6c5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c5k RCSB], [https://www.ebi.ac.uk/pdbsum/6c5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c5k ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q99LC4_MOUSE Q99LC4_MOUSE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Murine antibodies S25-23, S25-26 and S25-5 derive from a common germ-line origin and all bind the Chlamydiaceae family-specific epitope alphaKdo(2-->8)alphaKdo(2-->4)alphaKdo, (where Kdo is 3-deoxy-alpha-D-manno-oct-2-ulosonic acid) with high affinity and specificity. These antibodies recognize the entire trisaccharide antigen in a linkage dependent manner via a groove composed largely of germ-line residues. Despite sharing identical heavy and light chain genes, S25-23 binds the family-specific epitope with nanomolar affinity, which is an order of magnitude higher than S25-26, while S25-5 displays an affinity between that of S25-23 and S25-26. We determined the high resolution crystal structures of S25-23 and S25-5 antigen-binding fragments in complex with a pentasaccharide derived from the LPS of Chlamydia, and measured the affinity of S25-5 towards chlamydial LPS antigens using isothermal titration microcalorimetry. The 1.75 A resolution structure of S25-23 shows how subtle conservative mutations Arg(L)-27E to lysine and Ser(H)-56 to threonine lead to an order of magnitude increase in affinity. Importantly, comparison between previous S25-26 structures and the 1.99 and 2.05 A resolution liganded and unliganded structures of S25-5, respectively, shows how a Ser(L)-27E results in intermediate affinity due to reduced enthalpic penalty associated with complex formation that would otherwise be required for arginine in this position. This strategy allows for subtle adjustments in combining site via affinity maturation to lead to dramatic consequences in affinity of an antibody for its antigen. | |||
Subtle changes in the combining site of the Chlamydiaceae-specific mAb S25-23 increase antibody-carbohydrate binding affinity by an order of magnitude.,Haji-Ghassemi O, Muller-Loennies S, Brooks CL, MacKenzie CR, Caveney N, Van Petegem F, Brade L, Kosma P, Brade H, Evans SV Biochemistry. 2018 Dec 20. doi: 10.1021/acs.biochem.8b00318. PMID:30571096<ref>PMID:30571096</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Evans | <div class="pdbe-citations 6c5k" style="background-color:#fffaf0;"></div> | ||
[[Category: Haji-Ghassemi | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Evans SV]] | |||
[[Category: Haji-Ghassemi O]] | |||
Latest revision as of 17:56, 4 October 2023
S25-23 Fab in complex with Chlamydiaceae LPS (Crystal form 2)S25-23 Fab in complex with Chlamydiaceae LPS (Crystal form 2)
Structural highlights
FunctionPublication Abstract from PubMedMurine antibodies S25-23, S25-26 and S25-5 derive from a common germ-line origin and all bind the Chlamydiaceae family-specific epitope alphaKdo(2-->8)alphaKdo(2-->4)alphaKdo, (where Kdo is 3-deoxy-alpha-D-manno-oct-2-ulosonic acid) with high affinity and specificity. These antibodies recognize the entire trisaccharide antigen in a linkage dependent manner via a groove composed largely of germ-line residues. Despite sharing identical heavy and light chain genes, S25-23 binds the family-specific epitope with nanomolar affinity, which is an order of magnitude higher than S25-26, while S25-5 displays an affinity between that of S25-23 and S25-26. We determined the high resolution crystal structures of S25-23 and S25-5 antigen-binding fragments in complex with a pentasaccharide derived from the LPS of Chlamydia, and measured the affinity of S25-5 towards chlamydial LPS antigens using isothermal titration microcalorimetry. The 1.75 A resolution structure of S25-23 shows how subtle conservative mutations Arg(L)-27E to lysine and Ser(H)-56 to threonine lead to an order of magnitude increase in affinity. Importantly, comparison between previous S25-26 structures and the 1.99 and 2.05 A resolution liganded and unliganded structures of S25-5, respectively, shows how a Ser(L)-27E results in intermediate affinity due to reduced enthalpic penalty associated with complex formation that would otherwise be required for arginine in this position. This strategy allows for subtle adjustments in combining site via affinity maturation to lead to dramatic consequences in affinity of an antibody for its antigen. Subtle changes in the combining site of the Chlamydiaceae-specific mAb S25-23 increase antibody-carbohydrate binding affinity by an order of magnitude.,Haji-Ghassemi O, Muller-Loennies S, Brooks CL, MacKenzie CR, Caveney N, Van Petegem F, Brade L, Kosma P, Brade H, Evans SV Biochemistry. 2018 Dec 20. doi: 10.1021/acs.biochem.8b00318. PMID:30571096[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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