3ZPO

Crystal structure of JmjC domain of human histone demethylase UTY with bound GSK J1

PDB DOI: https://doi.org/10.2210/pdb3ZPO/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2013-02-28 Released: 2013-05-29
Deposition Author(s): Vollmar, M., Gileadi, C., Shrestha, L., Goubin, S., Johansson, C., Krojer, T., von Delft, F., Arrowsmith, C.H., Bountra, C., Edwards, A., Oppermann, U.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 ?
R-Value Free: 0.210
R-Value Work: 0.177
R-Value Observed: 0.179

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Human Uty(Kdm6C) is a Male-Specific Nepislon-Methyl Lysyl Demethylase.

Walport, L.J., Hopkinson, R.J., Vollmar, M., Madden, S.K., Gileadi, C., Oppermann, U., Schofield, C.J., Johansson, C.

(2014) J Biol Chem 289: 18302

PubMed: 24798337 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1074/jbc.M114.555052
Primary Citation of Related Structures:
3ZLI, 3ZPO

PubMed Abstract:
The Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenases. KDM6A (UTX) and KDM6B (JMJD3) are KDM6 subfamily members that catalyze demethylation of N(?)-methylated histone 3 lysine 27 (H3K27), a mark important for transcriptional repression. Despite reports stating that UTY(KDM6C) is inactive as a KDM, we demonstrate by biochemical studies, employing MS and NMR, that UTY(KDM6C) is an active KDM. Crystallographic analyses reveal that the UTY(KDM6C) active site is highly conserved with those of KDM6B and KDM6A. UTY(KDM6C) catalyzes demethylation of H3K27 peptides in vitro, analogously to KDM6B and KDM6A, but with reduced activity, due to point substitutions involved in substrate binding. The results expand the set of human KDMs and will be of use in developing selective KDM inhibitors.

Organizational Affiliation

From the Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom.

Macromolecule Content

Total Structure Weight: 112.09 kDa
Atom Count: 7,805
Modelled Residue Count: 881
Deposited Residue Count: 956
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
HISTONE DEMETHYLASE UTY	A, B	478	Homo sapiens	Mutation(s): 0 EC: 1.14.11.68
UniProt & NIH Common Fund Data Resources
Find proteins for O14607 (Homo sapiens) Explore O14607 Go to UniProtKB: O14607
PHAROS: O14607 GTEx: ENSG00000183878
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	O14607
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
K0I Query on K0I Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain O [auth B] MOL2 format, chain C [auth A] MOL2 format, chain O [auth B] mmCIF format, chain C [auth A] mmCIF format, chain O [auth B]	C [auth A], O [auth B]	3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoic acid C₂₂ H₂₃ N₅ O₂ AVZCPICCWKMZDT-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain O [auth B] Interactions & Density Focus chain C [auth A] Focus chain O [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain Q [auth B] MOL2 format, chain D [auth A] MOL2 format, chain Q [auth B] mmCIF format, chain D [auth A] mmCIF format, chain Q [auth B]	D [auth A], Q [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain Q [auth B] Interactions & Density Focus chain D [auth A] Focus chain Q [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] 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 R [auth B] SDF format, chain S [auth B] SDF format, chain T [auth B] SDF format, chain U [auth B] SDF format, chain V [auth B] SDF format, chain W [auth B] SDF format, chain X [auth B] SDF format, chain Y [auth B] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] 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 R [auth B] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] MOL2 format, chain V [auth B] MOL2 format, chain W [auth B] MOL2 format, chain X [auth B] MOL2 format, chain Y [auth B] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain K [auth A] mmCIF format, chain L [auth A] mmCIF format, chain M [auth A] mmCIF format, chain N [auth A] mmCIF format, chain R [auth B] mmCIF format, chain S [auth B] mmCIF format, chain T [auth B] mmCIF format, chain U [auth B] mmCIF format, chain V [auth B] mmCIF format, chain W [auth B] mmCIF format, chain X [auth B] mmCIF format, chain Y [auth B]	F [auth A] G [auth A] H [auth A] I [auth A] J [auth A] F [auth A], G [auth A], H [auth A], I [auth A], J [auth A], K [auth A], L [auth A], M [auth A], N [auth A], R [auth B], S [auth B], T [auth B], U [auth B], V [auth B], W [auth B], X [auth B], Y [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] 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 B] Focus chain Y [auth B] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] 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 B] Focus chain Y [auth B]
FE2 Query on FE2 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain P [auth B] MOL2 format, chain E [auth A] MOL2 format, chain P [auth B] mmCIF format, chain E [auth A] mmCIF format, chain P [auth B]	E [auth A], P [auth B]	FE (II) ION Fe CWYNVVGOOAEACU-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain P [auth B] Interactions & Density Focus chain E [auth A] Focus chain P [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
K0I	BindingDB: 3ZPO	IC50: min: 3200, max: 6.90e+4 (nM) from 2 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 ?
R-Value Free: 0.210
R-Value Work: 0.177
R-Value Observed: 0.179
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( ? )	Angle ( ? )
a = 91.158	α = 90
b = 110.755	β = 90
c = 119.492	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
Aimless	data scaling
PHASER	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2013-05-29

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2013-05-29
Type: Initial release
Version 1.1: 2014-01-29
Changes: Atomic model, Derived calculations, Non-polymer description
Version 1.2: 2015-05-20
Changes: Database references, Other
Version 1.3: 2023-12-20
Changes: Data collection, Database references, Derived calculations, Other, Refinement description