5L0V

human POGLUT1 in complex with 2F-glucose modified EGF(+) and UDP

Summary for 5L0V

• Entry DOI: 10.2210/pdb5l0v/pdb
• Related: 5L0R 5L0S 5L0T 5L0U
• Descriptor: Protein O-glucosyltransferase 1, EGF(+), 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: transferase glycosyltransferase gt-b glucosyltransferase, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 47962.08

Authors

Li, Z.,Rini, J.M. (deposition date: 2016-07-28, release date: 2017-08-09, Last modification date: 2024-10-23)

Primary citation

Li, Z.,Fischer, M.,Satkunarajah, M.,Zhou, D.,Withers, S.G.,Rini, J.M.
Structural basis of Notch O-glucosylation and O-xylosylation by mammalian protein-O-glucosyltransferase 1 (POGLUT1).
Nat Commun, 8:185-185, 2017

PubMed Abstract: Protein O-glucosyltransferase 1/Rumi-mediated glucosylation of Notch epidermal growth factor-like (EGF-like) domains plays an important role in Notch signaling. Protein O-glucosyltransferase 1 shows specificity for folded EGF-like domains, it can only glycosylate serine residues in the CXSXPC motif, and it possesses an uncommon dual donor substrate specificity. Using several EGF-like domains and donor substrate analogs, we have determined the structures of human Protein O-glucosyltransferase 1 substrate/product complexes that provide mechanistic insight into the basis for these properties. Notably, we show that Protein O-glucosyltransferase 1's requirement for folded EGF-like domains also leads to its serine specificity and that two distinct local conformational states are likely responsible for its ability to transfer both glucose and xylose. We also show that Protein O-glucosyltransferase 1 possesses the potential to xylosylate a much broader range of EGF-like domain substrates than was previously thought. Finally, we show that Protein O-glucosyltransferase 1 has co-evolved with EGF-like domains of the type found in Notch.POGLUT1 is a protein-O-glucosyltransferase that transfers glucose and xylose to the EGF-like domains of Notch and other signaling receptors. Here the authors report the structure of human POGLUT1 in complexes with 3 different EGF-like domains and donor substrates and shed light on the enzyme's substrate specificity and catalytic mechanism.

PubMed: 28775322
DOI: 10.1038/s41467-017-00255-7

Experimental method

X-RAY DIFFRACTION (1.305 Å)