PDBsum entry 3pe3

Transferase

PDB id: 3pe3

Contents

Protein chains

701 a.a. *

Ligands

UDP ×4

Waters ×265

* Residue conservation analysis

PDB id:

3pe3

Name:

Transferase

Title:

Structure of human o-glcnac transferase and its complex with a peptide substrate

Structure:

Udp-n-acetylglucosamine--peptide n- acetylglucosaminyltransferase 110 kda subunit. Chain: a, b, c, d. Fragment: hogt4.5, unp residues 323-1041. Synonym: o-glcnac transferase subunit p110, o-linked n- acetylglucosamine transferase 110 kda subunit. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ogt. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.78Å R-factor: 0.185 R-free: 0.218

Authors:

M.B.Lazarus,Y.Nam,J.Jiang,P.Sliz,S.Walker

Key ref:

M.B.Lazarus et al. (2011). Structure of human O-GlcNAc transferase and its complex with a peptide substrate. Nature, 469, 564-567. PubMed id: 21240259

Date:

25-Oct-10 Release date: 19-Jan-11

Protein chains

O15294  (OGT1_HUMAN) -  UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit from Homo sapiens

Seq: 1046 a.a.

Struc: 701 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.4.1.255 - protein O-GlcNAc transferase.
• Reaction:
  1. L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl- beta-D-glucosaminyl)-L-seryl-[protein] + UDP + H⁺
  2. L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O- (N-acetyl-beta-D-glucosaminyl)-L-threonyl-[protein] + UDP + H⁺

L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl- beta-D-glucosaminyl)-L-seryl-[protein] + UDP + H(+) (Bound ligand (Het Group name = UDP) corresponds exactly)

L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O- (N-acetyl-beta-D-glucosaminyl)-L-threonyl-[protein] + UDP + H(+) (Bound ligand (Het Group name = UDP) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Nature 469:564-567 (2011)

PubMed id: 21240259

Structure of human O-GlcNAc transferase and its complex with a peptide substrate.

M.B.Lazarus, Y.Nam, J.Jiang, P.Sliz, S.Walker.

ABSTRACT

The essential mammalian enzyme O-linked β-N-acetylglucosamine transferase (O-GlcNAc transferase, here OGT) couples metabolic status to the regulation of a wide variety of cellular signalling pathways by acting as a nutrient sensor. OGT catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine (UDP-GlcNAc) to serines and threonines of cytoplasmic, nuclear and mitochondrial proteins, including numerous transcription factors, tumour suppressors, kinases, phosphatases and histone-modifying proteins. Aberrant glycosylation by OGT has been linked to insulin resistance, diabetic complications, cancer and neurodegenerative diseases including Alzheimer's. Despite the importance of OGT, the details of how it recognizes and glycosylates its protein substrates are largely unknown. We report here two crystal structures of human OGT, as a binary complex with UDP (2.8 Å resolution) and as a ternary complex with UDP and a peptide substrate (1.95 Å). The structures provide clues to the enzyme mechanism, show how OGT recognizes target peptide sequences, and reveal the fold of the unique domain between the two halves of the catalytic region. This information will accelerate the rational design of biological experiments to investigate OGT's functions; it will also help the design of inhibitors for use as cellular probes and help to assess its potential as a therapeutic target.