8a49: Difference between revisions

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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/Q9APG4_STRPY Q9APG4_STRPY]  
[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__
__TOC__
</StructureSection>
</StructureSection>

Latest revision as of 10:00, 21 November 2024

Endoglycosidase S in complex with IgG1 FcEndoglycosidase S in complex with IgG1 Fc

Structural highlights

8a49 is a 4 chain structure with sequence from Homo sapiens and Streptococcus pyogenes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.45Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]

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[15]

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

References

  1. ↑ Collin M, Olsén A. EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG. EMBO J. 2001 Jun 15;20(12):3046-55. PMID:11406581 doi:10.1093/emboj/20.12.3046
  2. ↑ Collin M, Olsén A. Effect of SpeB and EndoS from Streptococcus pyogenes on human immunoglobulins. Infect Immun. 2001 Nov;69(11):7187-9. PMID:11598100 doi:10.1128/IAI.69.11.7187-7189.2001
  3. ↑ Collin M, Svensson MD, Sjöholm AG, Jensenius JC, Sjöbring U, Olsén A. EndoS and SpeB from Streptococcus pyogenes inhibit immunoglobulin-mediated opsonophagocytosis. Infect Immun. 2002 Dec;70(12):6646-51. PMID:12438337 doi:10.1128/IAI.70.12.6646-6651.2002
  4. ↑ Allhorn M, Olsén A, Collin M. EndoS from Streptococcus pyogenes is hydrolyzed by the cysteine proteinase SpeB and requires glutamic acid 235 and tryptophans for IgG glycan-hydrolyzing activity. BMC Microbiol. 2008 Jan 8;8:3. PMID:18182097 doi:10.1186/1471-2180-8-3
  5. ↑ Allhorn M, Briceño JG, Baudino L, Lood C, Olsson ML, Izui S, Collin M. The IgG-specific endoglycosidase EndoS inhibits both cellular and complement-mediated autoimmune hemolysis. Blood. 2010 Jun 17;115(24):5080-8. PMID:20357243 doi:10.1182/blood-2009-08-239020
  6. ↑ Sjögren J, Okumura CY, Collin M, Nizet V, Hollands A. Study of the IgG endoglycosidase EndoS in group A streptococcal phagocyte resistance and virulence. BMC Microbiol. 2011 May 27;11:120. PMID:21619648 doi:10.1186/1471-2180-11-120
  7. ↑ Goodfellow JJ, Baruah K, Yamamoto K, Bonomelli C, Krishna B, Harvey DJ, Crispin M, Scanlan CN, Davis BG. An endoglycosidase with alternative glycan specificity allows broadened glycoprotein remodelling. J Am Chem Soc. 2012 May 16;134(19):8030-3. PMID:22551167 doi:10.1021/ja301334b
  8. ↑ Huang W, Giddens J, Fan SQ, Toonstra C, Wang LX. Chemoenzymatic glycoengineering of intact IgG antibodies for gain of functions. J Am Chem Soc. 2012 Jul 25;134(29):12308-18. PMID:22747414 doi:10.1021/ja3051266
  9. ↑ Dixon EV, Claridge JK, Harvey DJ, Baruah K, Yu X, Vesiljevic S, Mattick S, Pritchard LK, Krishna B, Scanlan CN, Schnell JR, Higgins MK, Zitzmann N, Crispin M. Fragments of bacterial endoglycosidase s and immunoglobulin g reveal subdomains of each that contribute to deglycosylation. J Biol Chem. 2014 May 16;289(20):13876-89. PMID:24668806 doi:10.1074/jbc.M113.532812
  10. ↑ Trastoy B, Lomino JV, Pierce BG, Carter LG, Gunther S, Giddens JP, Snyder GA, Weiss TM, Weng Z, Wang LX, Sundberg EJ. Crystal structure of Streptococcus pyogenes EndoS, an immunomodulatory endoglycosidase specific for human IgG antibodies. Proc Natl Acad Sci U S A. 2014 May 6;111(18):6714-9. doi:, 10.1073/pnas.1322908111. Epub 2014 Apr 21. PMID:24753590 doi:http://dx.doi.org/10.1073/pnas.1322908111
  11. ↑ Sjögren J, Cosgrave EF, Allhorn M, Nordgren M, Björk S, Olsson F, Fredriksson S, Collin M. EndoS and EndoS2 hydrolyze Fc-glycans on therapeutic antibodies with different glycoform selectivity and can be used for rapid quantification of high-mannose glycans. Glycobiology. 2015 Oct;25(10):1053-63. PMID:26156869 doi:10.1093/glycob/cwv047
  12. ↑ Trastoy B, Klontz E, Orwenyo J, Marina A, Wang LX, Sundberg EJ, Guerin ME. Structural basis for the recognition of complex-type N-glycans by Endoglycosidase S. Nat Commun. 2018 May 14;9(1):1874. doi: 10.1038/s41467-018-04300-x. PMID:29760474 doi:http://dx.doi.org/10.1038/s41467-018-04300-x
  13. ↑ Tong X, Li T, Li C, Wang LX. Generation and Comparative Kinetic Analysis of New Glycosynthase Mutants from Streptococcus pyogenes Endoglycosidases for Antibody Glycoengineering. Biochemistry. 2018 Sep 4;57(35):5239-5246. PMID:30102520 doi:10.1021/acs.biochem.8b00719
  14. ↑ Naegeli A, Bratanis E, Karlsson C, Shannon O, Kalluru R, Linder A, Malmström J, Collin M. Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis. J Exp Med. 2019 Jul 1;216(7):1615-1629. PMID:31092533 doi:10.1084/jem.20190293
  15. ↑ Sudol ASL, Butler J, Ivory DP, Tews I, Crispin M. Extensive substrate recognition by the streptococcal antibody-degrading enzymes IdeS and EndoS. Nat Commun. 2022 Dec 17;13(1):7801. PMID:36528711 doi:10.1038/s41467-022-35340-z

8a49, resolution 3.45Å

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