4XIF

Human OGT in complex with UDP-5S-GlcNAc and substrate peptide (keratin-7)

Summary for 4XIF

• Entry DOI: 10.2210/pdb4xif/pdb
• Descriptor: UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit, Keratin, type II cytoskeletal 7, SULFATE ION, ... (4 entities in total)
• Functional Keywords: o-glcnac transferase inverting gt-b substrate complex, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Isoform 2: Mitochondrion. Isoform 3: Cytoplasm. Isoform 4: Cytoplasm: O15294; Cytoplasm : P08729
• Total number of polymer chains: 8
• Total formula weight: 330976.55

Authors

Schimpl, M.,van Aalten, D.M.F. (deposition date: 2015-01-06, release date: 2015-08-05, Last modification date: 2024-05-08)

Primary citation

Pathak, S.,Alonso, J.,Schimpl, M.,Rafie, K.,Blair, D.E.,Borodkin, V.S.,Schuttelkopf, A.W.,Albarbarawi, O.,van Aalten, D.M.
The active site of O-GlcNAc transferase imposes constraints on substrate sequence.
Nat.Struct.Mol.Biol., 22:744-750, 2015

PubMed Abstract: O-GlcNAc transferase (OGT) glycosylates a diverse range of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc), an essential and dynamic post-translational modification in metazoans. Although this enzyme modifies hundreds of proteins with O-GlcNAc, it is not understood how OGT achieves substrate specificity. In this study, we describe the application of a high-throughput OGT assay to a library of peptides. We mapped sites of O-GlcNAc modification by electron transfer dissociation MS and found that they correlate with previously detected O-GlcNAc sites. Crystal structures of four acceptor peptides in complex with Homo sapiens OGT suggest that a combination of size and conformational restriction defines sequence specificity in the -3 to +2 subsites. This work reveals that although the N-terminal TPR repeats of OGT may have roles in substrate recognition, the sequence restriction imposed by the peptide-binding site makes a substantial contribution to O-GlcNAc site specificity.

PubMed: 26237509
DOI: 10.1038/nsmb.3063

Experimental method

X-RAY DIFFRACTION (3.2 Å)