6mds

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Streptococcus pyogenes endo-beta-N-acetylglucosaminidase (EndoS2) with complex biantennary glycan

Structural highlights

6mds is a 2 chain structure with sequence from Streptococcus pyogenes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ENDS2_STRP9 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:23865566, PubMed:27288408, PubMed:26156869, PubMed:30937380). 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 (By similarity). Also able to cleave biantennary and sialylated glycans of host alpha-1-acid glycoprotein (ORM1 or ORM2) (PubMed:23865566, PubMed:27288408). Acts on N-linked glycans with or without core fucosylation (PubMed:26156869, PubMed:27288408, PubMed:30937380). In contrast to EndoS, also able to process oligomannose- or hybrid-type glycans (PubMed:26156869, PubMed:30937380). Specifically acts on IgGs; does not act on immunoglobulin alpha, beta, delta or mu (PubMed:26156869).[UniProtKB:Q99Y92]^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Immunoglobulin G (IgG) glycosylation critically modulates antibody effector functions. Streptococcus pyogenes secretes a unique endo-beta-N-acetylglucosaminidase, EndoS2, which deglycosylates the conserved N-linked glycan at Asn297 on IgG Fc to eliminate its effector functions and evade the immune system. EndoS2 and specific point mutants have been used to chemoenzymatically synthesize antibodies with customizable glycosylation for gain of functions. EndoS2 is useful in these schemes because it accommodates a broad range of N-glycans, including high-mannose, complex, and hybrid types; however, its mechanism of substrate recognition is poorly understood. We present crystal structures of EndoS2 alone and bound to complex and high-mannose glycans; the broad N-glycan specificity is governed by critical loops that shape the binding site of EndoS2. Furthermore, hydrolytic experiments, domain-swap chimeras, and hydrogen-deuterium exchange mass spectrometry reveal the importance of the carbohydrate-binding module in the mechanism of IgG recognition by EndoS2, providing insights into engineering enzymes to catalyze customizable glycosylation reactions.

Molecular Basis of Broad Spectrum N-Glycan Specificity and Processing of Therapeutic IgG Monoclonal Antibodies by Endoglycosidase S2.,Klontz EH, Trastoy B, Deredge D, Fields JK, Li C, Orwenyo J, Marina A, Beadenkopf R, Gunther S, Flores J, Wintrode PL, Wang LX, Guerin ME, Sundberg EJ ACS Cent Sci. 2019 Mar 27;5(3):524-538. doi: 10.1021/acscentsci.8b00917. Epub, 2019 Feb 6. PMID:30937380^[5]

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

References

↑ Sjögren J, Struwe WB, Cosgrave EF, Rudd PM, Stervander M, Allhorn M, Hollands A, Nizet V, Collin M. EndoS2 is a unique and conserved enzyme of serotype M49 group A Streptococcus that hydrolyses N-linked glycans on IgG and α1-acid glycoprotein. Biochem J. 2013 Oct 1;455(1):107-18. PMID:23865566 doi:10.1042/BJ20130126
↑ 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
↑ Li T, Tong X, Yang Q, Giddens JP, Wang LX. Glycosynthase Mutants of Endoglycosidase S2 Show Potent Transglycosylation Activity and Remarkably Relaxed Substrate Specificity for Antibody Glycosylation Remodeling. J Biol Chem. 2016 Aug 5;291(32):16508-18. PMID:27288408 doi:10.1074/jbc.M116.738765
↑ Klontz EH, Trastoy B, Deredge D, Fields JK, Li C, Orwenyo J, Marina A, Beadenkopf R, Gunther S, Flores J, Wintrode PL, Wang LX, Guerin ME, Sundberg EJ. Molecular Basis of Broad Spectrum N-Glycan Specificity and Processing of Therapeutic IgG Monoclonal Antibodies by Endoglycosidase S2. ACS Cent Sci. 2019 Mar 27;5(3):524-538. doi: 10.1021/acscentsci.8b00917. Epub, 2019 Feb 6. PMID:30937380 doi:http://dx.doi.org/10.1021/acscentsci.8b00917
↑ Klontz EH, Trastoy B, Deredge D, Fields JK, Li C, Orwenyo J, Marina A, Beadenkopf R, Gunther S, Flores J, Wintrode PL, Wang LX, Guerin ME, Sundberg EJ. Molecular Basis of Broad Spectrum N-Glycan Specificity and Processing of Therapeutic IgG Monoclonal Antibodies by Endoglycosidase S2. ACS Cent Sci. 2019 Mar 27;5(3):524-538. doi: 10.1021/acscentsci.8b00917. Epub, 2019 Feb 6. PMID:30937380 doi:http://dx.doi.org/10.1021/acscentsci.8b00917

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='6mds' size='340' side='right'caption='[[6mds]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mds]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"micrococcus_scarlatinae"_klein_1884 "micrococcus scarlatinae" klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MDS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mds]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MDS FirstGlance]. <br>
-</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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.5&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ndoS2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1314 "Micrococcus scarlatinae" Klein 1884])</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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</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=6mds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mds OCA], [https://pdbe.org/6mds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mds RCSB], [https://www.ebi.ac.uk/pdbsum/6mds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mds ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/ENDS2_STRP9 ENDS2_STRP9] 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:23865566, PubMed:27288408, PubMed:26156869, PubMed:30937380). 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 (By similarity). Also able to cleave biantennary and sialylated glycans of host alpha-1-acid glycoprotein (ORM1 or ORM2) (PubMed:23865566, PubMed:27288408). Acts on N-linked glycans with or without core fucosylation (PubMed:26156869, PubMed:27288408, PubMed:30937380). In contrast to EndoS, also able to process oligomannose- or hybrid-type glycans (PubMed:26156869, PubMed:30937380). Specifically acts on IgGs; does not act on immunoglobulin alpha, beta, delta or mu (PubMed:26156869).[UniProtKB:Q99Y92]<ref>PMID:23865566</ref> <ref>PMID:26156869</ref> <ref>PMID:27288408</ref> <ref>PMID:30937380</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Micrococcus scarlatinae klein 1884]]
 [[Category: Large Structures]]
-[[Category: Guerin, M E]]
+[[Category: Streptococcus pyogenes]]
-[[Category: Klontz, E H]]
+[[Category: Guerin ME]]
-[[Category: Orwenyo, J]]
+[[Category: Klontz EH]]
-[[Category: Sundberg, E J]]
+[[Category: Orwenyo J]]
-[[Category: Trastoy, B]]
+[[Category: Sundberg EJ]]
-[[Category: Wang, L X]]
+[[Category: Trastoy B]]
-[[Category: Endo-beta-n-acetylglucosaminidase s2]]
+[[Category: Wang LX]]
-[[Category: Endoglycosidase s2]]
-[[Category: Endos2]]
-[[Category: Glycoside hydrolase]]
-[[Category: Hydrolase]]

6mds

From Proteopedia

Current revision

Crystal structure of Streptococcus pyogenes endo-beta-N-acetylglucosaminidase (EndoS2) with complex biantennary glycan

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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