4pqg
From Proteopedia
Crystal structure of the pneumococcal O-GlcNAc transferase GtfA in complex with UDP and GlcNAc
Structural highlights
FunctionGTFA_STRPN Required for the polymorphic O-glycosylation of serine-rich repeat protein PsrP. Catalyzes the first step in glycosylation by transferring N-acetylglucosamine from UDP-GlcNAc to serine residues in PsrP (PubMed:24936067, PubMed:28246170). Part of the accessory SecA2/SecY2 system specifically required to export serine-rich repeat cell wall proteins encoded upstream in the same operon (Probable). The GtfA-GtfB complex adds GlcNAc from UDP-GlcNAc to PsrP (experimentally characterized with truncated PsrP-SSR1 constructs); this subunit alone has weak N-acetylglucosaminyl transferase activity that is 10-fold stimulated by GtfB. The complex requires at least a 25 residue-long peptide for activity; the in vitro assay has only been seen to glycosylate Ser residues (PubMed:24936067). The alpha linkage was shown in L.reuteri.[UniProtKB:A0A0S4NM89][1] [2] [3] Publication Abstract from PubMedProtein glycosylation catalyzed by the O-GlcNAc transferase (OGT) plays a critical role in various biological processes. In Streptococcus pneumoniae, the core enzyme GtfA and co-activator GtfB form an OGT complex to glycosylate the serine-rich repeat (SRR) of adhesin PsrP (pneumococcal serine-rich repeat protein), which is involved in the infection and pathogenesis. Here we report the 2.0 A crystal structure of GtfA, revealing a beta-meander add-on domain beyond the catalytic domain. It represents a novel add-on domain, which is distinct from the all-alpha-tetratricopeptide repeats in the only two structure-known OGTs. Structural analyses combined with binding assays indicate that this add-on domain contributes to forming an active GtfA-GtfB complex and recognizing the acceptor protein. In addition, the in vitro glycosylation system enables us to map the O-linkages to the serine residues within the first SRR of PsrP. These findings suggest that fusion with an add-on domain might be a universal mechanism for diverse OGTs that recognize varying acceptor proteins/peptides. Structure of a Novel O-Linked N-Acetyl-d-glucosamine (O-GlcNAc) Transferase, GtfA, Reveals Insights into the Glycosylation of Pneumococcal Serine-rich Repeat Adhesins.,Shi WW, Jiang YL, Zhu F, Yang YH, Shao QY, Yang HB, Ren YM, Wu H, Chen Y, Zhou CZ J Biol Chem. 2014 Jul 25;289(30):20898-20907. Epub 2014 Jun 16. PMID:24936067[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Large Structures | Streptococcus pneumoniae TIGR4 | Chen Y | Jiang YL | Ren YM | Shi WW | Wu H | Yang YH | Zhou CZ | Zhu F
