4AY6

Human O-GlcNAc transferase (OGT) in complex with UDP-5SGlcNAc and substrate peptide

PDB DOI: https://doi.org/10.2210/pdb4AY6/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21
Mutation(s): No

Deposited: 2012-06-18 Released: 2012-10-24
Deposition Author(s): Schimpl, M., Zheng, X., Blair, D.E., Schuettelkopf, A.W., Navratilova, I., Aristotelous, T., Ferenbach, A.T., Macnaughtan, M.A., Borodkin, V.S., van Aalten, D.M.F.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.30 ?
R-Value Free: 0.272
R-Value Work: 0.227
R-Value Observed: 0.227

wwPDB Validation 3D Report Full Report

This is version 1.2 of the entry. See complete history.

Literature

O-Glcnac Transferase Invokes Nucleotide Sugar Pyrophosphate Participation in Catalysis

Schimpl, M., Zheng, X., Borodkin, V.S., Blair, D.E., Ferenbach, A.T., Schuettelkopf, A.W., Navratilova, I., Aristotelous, T., Albarbarawi, O., Robinson, D.A., Macnaughtan, M.A., Van Aalten, D.M.F.

(2012) Nat Chem Biol 8: 969

PubMed: 23103942 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/nchembio.1108
Primary Citation of Related Structures:
4AY5, 4AY6

PubMed Abstract:
Protein O-GlcNAcylation is an essential post-translational modification on hundreds of intracellular proteins in metazoa, catalyzed by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) using unknown mechanisms of transfer and substrate recognition. Through crystallographic snapshots and mechanism-inspired chemical probes, we define how human OGT recognizes the sugar donor and acceptor peptide and uses a new catalytic mechanism of glycosyl transfer, involving the sugar donor α-phosphate as the catalytic base as well as an essential lysine. This mechanism seems to be a unique evolutionary solution to the spatial constraints imposed by a bulky protein acceptor substrate and explains the unexpected specificity of a recently reported metabolic OGT inhibitor.

Organizational Affiliation

College of Life Sciences, University of Dundee, Dundee, UK.

Macromolecule Content

Total Structure Weight: 332.01 kDa
Atom Count: 22,544
Modelled Residue Count: 2,836
Deposited Residue Count: 2,944
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
UDP-N-ACETYLGLUCOSAMINE--PEPTIDE N-ACETYLGLUCOSAMINYLTRANS FERASE 110 KDA SUBUNIT	A, B, C, D	723	Homo sapiens	Mutation(s): 0 EC: 2.4.1.255
UniProt & NIH Common Fund Data Resources
Find proteins for O15294 (Homo sapiens) Explore O15294 Go to UniProtKB: O15294
PHAROS: O15294 GTEx: ENSG00000147162
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O15294
Sequence Annotations Expand
Reference Sequence

Find similar proteins by: Sequence | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
TGF-BETA-ACTIVATED KINASE 1 AND MAP3K7-BINDING PROTEIN 1	E, F, G, H	13	Homo sapiens	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for Q15750 (Homo sapiens) Explore Q15750 Go to UniProtKB: Q15750
PHAROS: Q15750 GTEx: ENSG00000100324
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q15750
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
12V Query on 12V Download Ideal Coordinates CCD File SDF format, chain J [auth A] SDF format, chain L [auth B] SDF format, chain N [auth C] SDF format, chain P [auth D] MOL2 format, chain J [auth A] MOL2 format, chain L [auth B] MOL2 format, chain N [auth C] MOL2 format, chain P [auth D] mmCIF format, chain J [auth A] mmCIF format, chain L [auth B] mmCIF format, chain N [auth C] mmCIF format, chain P [auth D]	J [auth A], L [auth B], N [auth C], P [auth D]	(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 C₁₇ H₂₇ N₃ O₁₆ P₂ S JPRVHSQHWXZSNC-UBDZBXRQSA-N		Interactions Focus chain J [auth A] Focus chain L [auth B] Focus chain N [auth C] Focus chain P [auth D] Interactions & Density Focus chain J [auth A] Focus chain L [auth B] Focus chain N [auth C] Focus chain P [auth D]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain K [auth B] SDF format, chain M [auth C] SDF format, chain O [auth D] MOL2 format, chain I [auth A] MOL2 format, chain K [auth B] MOL2 format, chain M [auth C] MOL2 format, chain O [auth D] mmCIF format, chain I [auth A] mmCIF format, chain K [auth B] mmCIF format, chain M [auth C] mmCIF format, chain O [auth D]	I [auth A], K [auth B], M [auth C], O [auth D]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain I [auth A] Focus chain K [auth B] Focus chain M [auth C] Focus chain O [auth D] Interactions & Density Focus chain I [auth A] Focus chain K [auth B] Focus chain M [auth C] Focus chain O [auth D]