5BNW

The active site of O-GlcNAc transferase imposes constraints on substrate sequence

5BNW の概要

• エントリーDOI: 10.2210/pdb5bnw/pdb
• 分子名称: UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit, laminB1 residues 179-191, (2S,3R,4R,5S,6R)-3-(acetylamino)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-thiopyran-2-yl [(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl dihydrogen diphosphate, ... (4 entities in total)
• 機能のキーワード: o-glcnac transferase, glycosyl transferase, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Isoform 2: Mitochondrion. Isoform 3: Cytoplasm. Isoform 4: Cytoplasm: O15294
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 82944.46

構造登録者

Pathak, S.,Alonso, J.,Schimpl, M.,Rafie, K.,Blair, D.E.,Borodkin, V.S.,Albarbarawi, O.,van Aalten, D.M.F. (登録日: 2015-05-26, 公開日: 2015-08-05, 最終更新日: 2024-01-10)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)