7yx8: Difference between revisions
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==Crystal structure of the AM0627 (E326A) inactive mutant in complex with PSGL-1-like bis-T glycopeptide and Zn2+== | |||
<StructureSection load='7yx8' size='340' side='right'caption='[[7yx8]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7yx8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Akkermansia_muciniphila Akkermansia muciniphila] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YX8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YX8 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7yx8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yx8 OCA], [https://pdbe.org/7yx8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yx8 RCSB], [https://www.ebi.ac.uk/pdbsum/7yx8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yx8 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[https://www.uniprot.org/uniprot/B2UPI7_AKKM8 B2UPI7_AKKM8]] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mucinases of human gut bacteria cleave peptide bonds in mucins strictly depending on the presence of neighboring O-glycans. The Akkermansia muciniphila AM0627 mucinase cleaves specifically in between contiguous (bis) O-glycans of defined truncated structures, suggesting that this enzyme may recognize clustered O-glycan patches. Here, we report the structure and molecular mechanism of AM0627 in complex with a glycopeptide containing a bis-T (Galbeta1-3GalNAcalpha1-O-Ser/Thr) O-glycan, revealing that AM0627 recognizes both the sugar moieties and the peptide sequence. AM0627 exhibits preference for bis-T over bis-Tn (GalNAcalpha1-O-Ser/Thr) O-glycopeptide substrates, with the first GalNAc residue being essential for cleavage. AM0627 follows a mechanism relying on a nucleophilic water molecule and a catalytic base Glu residue. Structural comparison among mucinases identifies a conserved Tyr engaged in sugar-pi interactions in both AM0627 and the Bacteroides thetaiotaomicron BT4244 mucinase as responsible for the common activity of these two mucinases with bis-T/Tn substrates. Our work illustrates how mucinases through tremendous flexibility adapt to the diversity in distribution and patterns of O-glycans on mucins. | |||
Structural and mechanistic insights into the cleavage of clustered O-glycan patches-containing glycoproteins by mucinases of the human gut.,Taleb V, Liao Q, Narimatsu Y, Garcia-Garcia A, Companon I, Borges RJ, Gonzalez-Ramirez AM, Corzana F, Clausen H, Rovira C, Hurtado-Guerrero R Nat Commun. 2022 Jul 26;13(1):4324. doi: 10.1038/s41467-022-32021-9. PMID:35882872<ref>PMID:35882872</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7yx8" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Akkermansia muciniphila]] | ||
[[Category: Garcia-Garcia | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: | [[Category: Borges RJ]] | ||
[[Category: Rovira | [[Category: Clausen H]] | ||
[[Category: | [[Category: Companon I]] | ||
[[Category: Corzana F]] | |||
[[Category: Garcia-Garcia A]] | |||
[[Category: Gonzalez-Ramirez AM]] | |||
[[Category: Hurtado-Guerrero R]] | |||
[[Category: Liao Q]] | |||
[[Category: Narimatsu Y]] | |||
[[Category: Rovira C]] | |||
[[Category: Taleb V]] | |||
Latest revision as of 05:04, 8 September 2022
Crystal structure of the AM0627 (E326A) inactive mutant in complex with PSGL-1-like bis-T glycopeptide and Zn2+
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