6mds: Difference between revisions
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==Crystal structure of Streptococcus pyogenes endo-beta-N-acetylglucosaminidase (EndoS2) with complex biantennary glycan== | |||
<StructureSection load='6mds' size='340' side='right'caption='[[6mds]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6mds]] is a 2 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MDS FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ndoS2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1314 "Micrococcus scarlatinae" Klein 1884])</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=6mds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mds OCA], [http://pdbe.org/6mds PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mds RCSB], [http://www.ebi.ac.uk/pdbsum/6mds PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mds ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:30937380</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6mds" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Micrococcus scarlatinae klein 1884]] | |||
[[Category: Large Structures]] | |||
[[Category: Guerin, M E]] | |||
[[Category: Klontz, E H]] | |||
[[Category: Orwenyo, J]] | |||
[[Category: Sundberg, E J]] | |||
[[Category: Trastoy, B]] | [[Category: Trastoy, B]] | ||
[[Category: | [[Category: Wang, L X]] | ||
[[Category: | [[Category: Endo-beta-n-acetylglucosaminidase s2]] | ||
[[Category: | [[Category: Endoglycosidase s2]] | ||
[[Category: | [[Category: Endos2]] | ||
[[Category: | [[Category: Glycoside hydrolase]] | ||
[[Category: Hydrolase]] |