8a47: Difference between revisions
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==IdeS in complex with IgG1 Fc== | |||
<StructureSection load='8a47' size='340' side='right'caption='[[8a47]], [[Resolution|resolution]] 2.34Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8a47]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptococcus_pyogenes_serotype_M59 Streptococcus pyogenes serotype M59]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A47 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]] 2.338Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8a47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a47 OCA], [https://pdbe.org/8a47 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a47 RCSB], [https://www.ebi.ac.uk/pdbsum/8a47 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a47 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A8B6IYA1_STRPY A0A8B6IYA1_STRPY] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Enzymatic cleavage of IgG antibodies is a common strategy used by pathogenic bacteria to ablate immune effector function. The Streptococcus pyogenes bacterium secretes the protease IdeS and the glycosidase EndoS, which specifically catalyse cleavage and deglycosylation of human IgG, respectively. IdeS has received clinical approval for kidney transplantation in hypersensitised individuals, while EndoS has found application in engineering antibody glycosylation. We present crystal structures of both enzymes in complex with their IgG1 Fc substrate, which was achieved using Fc engineering to disfavour preferential Fc crystallisation. The IdeS protease displays extensive Fc recognition and encases the antibody hinge. Conversely, the glycan hydrolase domain in EndoS traps the Fc glycan in a "flipped-out" conformation, while additional recognition of the Fc peptide is driven by the so-called carbohydrate binding module. In this work, we reveal the molecular basis of antibody recognition by bacterial enzymes, providing a template for the development of next-generation enzymes. | |||
Extensive substrate recognition by the streptococcal antibody-degrading enzymes IdeS and EndoS.,Sudol ASL, Butler J, Ivory DP, Tews I, Crispin M Nat Commun. 2022 Dec 17;13(1):7801. doi: 10.1038/s41467-022-35340-z. PMID:36528711<ref>PMID:36528711</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8a47" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Crispin | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Streptococcus pyogenes serotype M59]] | |||
[[Category: Crispin M]] | |||
[[Category: Sudol ASL]] | |||
[[Category: Tews I]] | |||
Latest revision as of 14:51, 23 October 2024
IdeS in complex with IgG1 FcIdeS in complex with IgG1 Fc
Structural highlights
FunctionPublication Abstract from PubMedEnzymatic cleavage of IgG antibodies is a common strategy used by pathogenic bacteria to ablate immune effector function. The Streptococcus pyogenes bacterium secretes the protease IdeS and the glycosidase EndoS, which specifically catalyse cleavage and deglycosylation of human IgG, respectively. IdeS has received clinical approval for kidney transplantation in hypersensitised individuals, while EndoS has found application in engineering antibody glycosylation. We present crystal structures of both enzymes in complex with their IgG1 Fc substrate, which was achieved using Fc engineering to disfavour preferential Fc crystallisation. The IdeS protease displays extensive Fc recognition and encases the antibody hinge. Conversely, the glycan hydrolase domain in EndoS traps the Fc glycan in a "flipped-out" conformation, while additional recognition of the Fc peptide is driven by the so-called carbohydrate binding module. In this work, we reveal the molecular basis of antibody recognition by bacterial enzymes, providing a template for the development of next-generation enzymes. Extensive substrate recognition by the streptococcal antibody-degrading enzymes IdeS and EndoS.,Sudol ASL, Butler J, Ivory DP, Tews I, Crispin M Nat Commun. 2022 Dec 17;13(1):7801. doi: 10.1038/s41467-022-35340-z. PMID:36528711[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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