PDBsum entry 4n3b

Transferase/substrate

PDB id: 4n3b

Contents

Protein chains

697 a.a.

20 a.a.

Ligands

12V

Waters ×124

PDB id:

4n3b

Name:

Transferase/substrate

Title:

Crystal structure of human o-glcnac transferase bound to a peptide from hcf-1 pro-repeat2(1-26)e10q and udp-5sglcnac

Structure:

Udp-n-acetylglucosamine--peptide n- acetylglucosaminyltransferase 110 kda subunit. Chain: a. Fragment: unp residues 323-1041. Synonym: o-glcnac transferase subunit p110, o-linked n- acetylglucosamine transferase 110 kda subunit, ogt. Engineered: yes. Host cell factor 1. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ogt. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.17Å R-factor: 0.194 R-free: 0.223

Authors:

M.B.Lazarus,W.Herr,S.Walker

Key ref:

M.B.Lazarus et al. (2013). HCF-1 is cleaved in the active site of O-GlcNAc transferase. Science, 342, 1235-1239. PubMed id: 24311690 DOI: 10.1126/science.1243990

Date:

06-Oct-13 Release date: 01-Jan-14

Protein chain

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

Seq: 1046 a.a.

Struc: 697 a.a.

Protein chain

P51610  (HCFC1_HUMAN) -  Host cell factor 1 from Homo sapiens

Seq: 2035 a.a.

Struc: 20 a.a.*

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

Enzyme reactions

• Enzyme class: Chain A: 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 = 12V) matches with 64.10% similarity)

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 = 12V) matches with 64.10% similarity)

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

Added reference

DOI no: 10.1126/science.1243990

Science 342:1235-1239 (2013)

PubMed id: 24311690

HCF-1 is cleaved in the active site of O-GlcNAc transferase.

M.B.Lazarus, J.Jiang, V.Kapuria, T.Bhuiyan, J.Janetzko, W.F.Zandberg, D.J.Vocadlo, W.Herr, S.Walker.

ABSTRACT

Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The conformation is similar to that of a glycosylation-competent peptide substrate. Cleavage occurs between cysteine and glutamate residues and results in a pyroglutamate product. Conversion of the cleavage site glutamate into serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus, protein glycosylation and HCF-1 cleavage occur in the same active site.