View source for 8a49


==Endoglycosidase S in complex with IgG1 Fc==
<StructureSection load='8a49' size='340' side='right'caption='[[8a49]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8a49]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A49 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]] 3.45&#8491;</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=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=8a49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a49 OCA], [https://pdbe.org/8a49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a49 RCSB], [https://www.ebi.ac.uk/pdbsum/8a49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a49 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ENDOS_STRP1 ENDOS_STRP1] Endoglucosidase that acts as a host immune evasion factor by mediating hydrolysis of the N-linked glycan from the Fc region of host immunoglobulin-gamma (IgG) during infection (PubMed:11406581, PubMed:11598100, PubMed:12438337, PubMed:18182097, PubMed:20357243, PubMed:21619648, PubMed:22551167, PubMed:22747414, PubMed:24668806, PubMed:24753590, PubMed:29760474, PubMed:30102520, PubMed:31092533). Specifically catalyzes the hydrolysis of the beta-1,4 linkage between the first two N-acetylglucosamine residues of the complex-type N-linked glycan located on 'Asn-297' of the Fc region of IgG antibodies (IGHG1, IGHG2, IGHG3 or IGHG4), thereby preventing interaction between IgGs and Fc receptors and ability to activate the complement pathway (PubMed:11406581, PubMed:11598100, PubMed:12438337, PubMed:20357243, PubMed:21619648, PubMed:31092533). Shows a specificity for biantennary complex type N-glycans; does neither cleave larger complex type glycans nor oligomannose and nor hybrid-type glycans (PubMed:22551167, PubMed:26156869). Specifically acts on IgGs; does not act on immunoglobulin alpha, beta, delta or mu (PubMed:11598100).<ref>PMID:11406581</ref> <ref>PMID:11598100</ref> <ref>PMID:12438337</ref> <ref>PMID:18182097</ref> <ref>PMID:20357243</ref> <ref>PMID:21619648</ref> <ref>PMID:22551167</ref> <ref>PMID:22747414</ref> <ref>PMID:24668806</ref> <ref>PMID:24753590</ref> <ref>PMID:26156869</ref> <ref>PMID:29760474</ref> <ref>PMID:30102520</ref> <ref>PMID:31092533</ref> 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8a49" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Streptococcus pyogenes]]
[[Category: Crispin M]]
[[Category: Sudol ASL]]
[[Category: Tews I]]