4CDR

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

PDB DOI: https://doi.org/10.2210/pdb4CDR/pdb

Classification: TRANSFERASE/TRANSFERASE INHIBITOR
Organism(s): Homo sapiens, synthetic construct
Expression System: Escherichia coli BL21
Mutation(s): No

Deposited: 2013-11-05 Released: 2013-12-04
Deposition Author(s): Schimpl, M., Gundogdu, M., van Aalten, D.M.F.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.15 Å
R-Value Free: 0.213
R-Value Work: 0.197
R-Value Observed: 0.197

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Bisubstrate Udp-Peptide Conjugates as Human O-Glcnac Transferase Inhibitors.

Borodkin, V.S., Schimpl, M., Gundogdu, M., Rafie, K., Dorfmueller, H.C., Robinson, D.A., Van Aalten, D.M.

(2014) Biochem J 457: 497

PubMed: 24256146 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1042/BJ20131272
Primary Citation of Related Structures:
4CDR

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.

Organizational Affiliation

*MRC Protein Phosphorylation und Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, U.K.

Macromolecule Content

Total Structure Weight: 331.52 kDa
Atom Count: 22,523
Modelled Residue Count: 2,828
Deposited Residue Count: 2,928
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
UDP-N-ACETYLGLUCOSAMINE--PEPTIDE N-ACETYLGLUCOSAMINYLTRANSFERASE 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
GOBLIN1	E, F, G, H	9	synthetic construct	Mutation(s): 0
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
UDP Query on UDP Download Ideal Coordinates CCD File SDF format, chain KA [auth E] SDF format, chain MA [auth F] SDF format, chain OA [auth G] SDF format, chain PA [auth H] MOL2 format, chain KA [auth E] MOL2 format, chain MA [auth F] MOL2 format, chain OA [auth G] MOL2 format, chain PA [auth H]	KA [auth E], MA [auth F], OA [auth G], PA [auth H]	URIDINE-5'-DIPHOSPHATE C₉ H₁₄ N₂ O₁₂ P₂ XCCTYIAWTASOJW-XVFCMESISA-N		Interactions Focus chain KA [auth E] Focus chain MA [auth F] Focus chain OA [auth G] Focus chain PA [auth H] Interactions & Density Focus chain KA [auth E] Focus chain MA [auth F] Focus chain OA [auth G] Focus chain PA [auth H]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain BA [auth C] SDF format, chain DA [auth D] SDF format, chain FA [auth D] SDF format, chain GA [auth D] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain JA [auth D] SDF format, chain LA [auth E] SDF format, chain QA [auth H] SDF format, chain S [auth B] SDF format, chain U [auth B] SDF format, chain AA [auth C] SDF format, chain CA [auth C] SDF format, chain EA [auth D] SDF format, chain HA [auth D] SDF format, chain IA [auth D] SDF format, chain K [auth A] SDF format, chain L [auth A] SDF format, chain M [auth A] SDF format, chain N [auth A] SDF format, chain NA [auth F] SDF format, chain O [auth A] SDF format, chain P [auth A] SDF format, chain Q [auth B] SDF format, chain R [auth B] SDF format, chain T [auth B] SDF format, chain V [auth B] SDF format, chain W [auth B] SDF format, chain X [auth C] SDF format, chain Y [auth C] SDF format, chain Z [auth C] MOL2 format, chain BA [auth C] MOL2 format, chain DA [auth D] MOL2 format, chain FA [auth D] MOL2 format, chain GA [auth D] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain JA [auth D] MOL2 format, chain LA [auth E] MOL2 format, chain QA [auth H] MOL2 format, chain S [auth B] MOL2 format, chain U [auth B] MOL2 format, chain AA [auth C] MOL2 format, chain CA [auth C] MOL2 format, chain EA [auth D] MOL2 format, chain HA [auth D] MOL2 format, chain IA [auth D] MOL2 format, chain K [auth A] MOL2 format, chain L [auth A] MOL2 format, chain M [auth A] MOL2 format, chain N [auth A] MOL2 format, chain NA [auth F] MOL2 format, chain O [auth A] MOL2 format, chain P [auth A] MOL2 format, chain Q [auth B] MOL2 format, chain R [auth B] MOL2 format, chain T [auth B] MOL2 format, chain V [auth B] MOL2 format, chain W [auth B] MOL2 format, chain X [auth C] MOL2 format, chain Y [auth C] MOL2 format, chain Z [auth C]	AA [auth C] BA [auth C] CA [auth C] DA [auth D] EA [auth D] AA [auth C], BA [auth C], CA [auth C], DA [auth D], EA [auth D], FA [auth D], GA [auth D], HA [auth D], I [auth A], IA [auth D], J [auth A], JA [auth D], K [auth A], L [auth A], LA [auth E], M [auth A], N [auth A], NA [auth F], O [auth A], P [auth A], Q [auth B], QA [auth H], R [auth B], S [auth B], T [auth B], U [auth B], V [auth B], W [auth B], X [auth C], Y [auth C], Z [auth C]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain AA [auth C] Focus chain BA [auth C] Focus chain CA [auth C] Focus chain DA [auth D] Focus chain EA [auth D] Focus chain FA [auth D] Focus chain GA [auth D] Focus chain HA [auth D] Focus chain I [auth A] Focus chain IA [auth D] Focus chain J [auth A] Focus chain JA [auth D] Focus chain K [auth A] Focus chain L [auth A] Focus chain LA [auth E] Focus chain M [auth A] Focus chain N [auth A] Focus chain NA [auth F] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth B] Focus chain QA [auth H] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth C] Focus chain Y [auth C] Focus chain Z [auth C] Interactions & Density Focus chain AA [auth C] Focus chain BA [auth C] Focus chain CA [auth C] Focus chain DA [auth D] Focus chain EA [auth D] Focus chain FA [auth D] Focus chain GA [auth D] Focus chain HA [auth D] Focus chain I [auth A] Focus chain IA [auth D] Focus chain J [auth A] Focus chain JA [auth D] Focus chain K [auth A] Focus chain L [auth A] Focus chain LA [auth E] Focus chain M [auth A] Focus chain N [auth A] Focus chain NA [auth F] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth B] Focus chain QA [auth H] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth C] Focus chain Y [auth C] Focus chain Z [auth C]

Modified Residues 1 Unique
ID	Chains	Type	Formula	2D Diagram	Parent
SRZ Query on SRZ	E, F, G, H	L-PEPTIDE LINKING	C₆ H₁₃ N O₄		SER

Binding Affinity Annotations
ID	Source	Binding Affinity
UDP	BindingDB: 4CDR	IC50: 1800 (nM) from 1 assay(s)

Biologically Interesting Molecules (External Reference) 1 Unique

Entity ID: 2
ID	Chains	Name	Type/Class	2D Diagram	3D Interactions
PRD_002043 Query on PRD_002043	E, F, G, H	Goblin1	Peptide-like / Enzyme inhibitor		Interactions Focus chain E Focus chain F Focus chain G Focus chain H Interactions & Density Focus chain E Focus chain F Focus chain G Focus chain H

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.15 Å
R-Value Free: 0.213
R-Value Work: 0.197
R-Value Observed: 0.197
Space Group: P 3 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 273.728	α = 90
b = 273.728	β = 90
c = 142.581	γ = 120

Software Package:

Software Name	Purpose
REFMAC	refinement
xia2	data reduction
SCALA	data scaling
REFMAC	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2013-12-04

Deposition Author(s):

Schimpl, M.

Gundogdu, M.

van Aalten, D.M.F.

Revision History (Full details and data files)

Version 1.0: 2013-12-04
Type: Initial release
Version 1.1: 2014-01-29
Changes: Database references
Version 1.2: 2016-12-14
Changes: Source and taxonomy
Version 1.3: 2023-12-20
Changes: Data collection, Database references, Derived calculations, Other, Refinement description