4CDR

Human O-GlcNAc transferase in complex with a bisubstrate inhibitor, Goblin1

Summary for 4CDR

• Entry DOI: 10.2210/pdb4cdr/pdb
• Related PRD ID: PRD_002043
• Descriptor: UDP-N-ACETYLGLUCOSAMINE--PEPTIDE N-ACETYLGLUCOSAMINYLTRANSFERASE 110 KDA SUBUNIT, GOBLIN1, SULFATE ION, ... (4 entities in total)
• Functional Keywords: transferase-transferase inhibitor complex, inverting gt-b enzyme, bi-substrate analog inhibitor, transferase/transferase inhibitor
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Isoform 2: Mitochondrion. Isoform 3: Cytoplasm. Isoform 4: Cytoplasm: O15294
• Total number of polymer chains: 8
• Total formula weight: 331516.14

Authors

Schimpl, M.,Gundogdu, M.,van Aalten, D.M.F. (deposition date: 2013-11-05, release date: 2013-12-04, Last modification date: 2024-10-16)

Primary citation

Borodkin, V.S.,Schimpl, M.,Gundogdu, M.,Rafie, K.,Dorfmueller, H.C.,Robinson, D.A.,Van Aalten, D.M.
Bisubstrate Udp-Peptide Conjugates as Human O-Glcnac Transferase Inhibitors.
Biochem.J., 457:497-, 2014

PubMed Abstract: Inhibitors of OGT (O-GlcNAc transferase) are valuable tools to study the cell biology of protein O-GlcNAcylation. We report OGT bisubstrate-linked inhibitors (goblins) in which the acceptor serine in the peptide VTPVSTA is covalently linked to UDP, eliminating the GlcNAc pyranoside ring. Goblin1 co-crystallizes with OGT, revealing an ordered C₃ linker and retained substrate-binding modes, and binds the enzyme with micromolar affinity, inhibiting glycosyltransfer on to protein and peptide substrates.

PubMed: 24256146
DOI: 10.1042/BJ20131272

Experimental method

X-RAY DIFFRACTION (3.15 Å)