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6c5h

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S25-5 Fab in complex with Chlamydiaceae-specific LPS antigen

Structural highlights

6c5h is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.99Å
Ligands:	, , , , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q99LC4_MOUSE

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^[1]

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

References

↑ Haji-Ghassemi O, Muller-Loennies S, Brooks CL, MacKenzie CR, Caveney N, Van Petegem F, Brade L, Kosma P, Brade H, Evans SV. Subtle changes in the combining site of the Chlamydiaceae-specific mAb S25-23 increase antibody-carbohydrate binding affinity by an order of magnitude. Biochemistry. 2018 Dec 20. doi: 10.1021/acs.biochem.8b00318. PMID:30571096 doi:http://dx.doi.org/10.1021/acs.biochem.8b00318

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6c5h"

Categories: Large Structures | Mus musculus | Evans SV | Haji-Ghassemi O

@@ Line 3: / Line 3: @@
 <StructureSection load='6c5h' size='340' side='right'caption='[[6c5h]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6c5h]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C5H FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6c5h]] is a 2 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=6C5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C5H FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene>, <scene name='pdbligand=Z9M:2-AMINO-2-DEOXY-4-O-PHOSPHONO-BETA-D-GLUCOPYRANOSE'>Z9M</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]] 1.99&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6c5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c5h OCA], [http://pdbe.org/6c5h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c5h RCSB], [http://www.ebi.ac.uk/pdbsum/6c5h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c5h 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=6c5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c5h OCA], [https://pdbe.org/6c5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c5h RCSB], [https://www.ebi.ac.uk/pdbsum/6c5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c5h ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q99LC4_MOUSE Q99LC4_MOUSE]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 17: / Line 19: @@
 </div>
 <div class="pdbe-citations 6c5h" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 == References ==
 <references/>
@@ Line 23: / Line 28: @@
 [[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Evans, S V]]
+[[Category: Evans SV]]
-[[Category: Haji-Ghassemi, O]]
+[[Category: Haji-Ghassemi O]]
-[[Category: Antibody]]
-[[Category: Antigen]]
-[[Category: Chlamydia]]
-[[Category: Complex]]
-[[Category: Immune system]]
-[[Category: Lipopolysaccharide]]
-[[Category: Sugar binding protein]]

6c5h

From Proteopedia

Current revision

S25-5 Fab in complex with Chlamydiaceae-specific LPS antigen

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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