7yx8

Crystal structure of the AM0627 (E326A) inactive mutant in complex with PSGL-1-like bis-T glycopeptide and Zn2+

spinqualitylabelsall models 7yx8, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yx8 is a 4 chain structure with sequence from Akkermansia muciniphila and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: A2G, GAL, GOL, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [B2UPI7_AKKM8] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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