4TZ8

Structure of human ATAD2 bromodomain bound to fragment inhibitor

PDB DOI: https://doi.org/10.2210/pdb4TZ8/pdb

Classification: Hydrolase/Hydrolase inhibitor
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2014-07-09 Released: 2014-10-29
Deposition Author(s): Harner, M.J., Chauder, B.A., Phan, J., Fesik, S.W.
Funding Organization(s): National Institutes of Health/National Cancer Institute (NIH/NCI)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.15 Å
R-Value Free: 0.231
R-Value Work: 0.198
R-Value Observed: 0.202

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.6 of the entry. See complete history.

Literature

Fragment-Based Screening of the Bromodomain of ATAD2.

Harner, M.J., Chauder, B.A., Phan, J., Fesik, S.W.

(2014) J Med Chem 57: 9687-9692

PubMed: 25314628 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1021/jm501035j
Primary Citation of Related Structures:
4TYL, 4TZ2, 4TZ8

PubMed Abstract:
Cellular and genetic evidence suggest that inhibition of ATAD2 could be a useful strategy to treat several types of cancer. To discover small-molecule inhibitors of the bromodomain of ATAD2, we used a fragment-based approach. Fragment hits were identified using NMR spectroscopy, and ATAD2 was crystallized with three of the hits identified in the fragment screen.

Organizational Affiliation

Department of Biochemistry, Vanderbilt University School of Medicine , 2215 Garland Avenue, 607 Light Hall, Nashville, Tennessee 37232-0146, United States.

Macromolecule Content

Total Structure Weight: 15.89 kDa
Atom Count: 1,229
Modelled Residue Count: 130
Deposited Residue Count: 130
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
ATPase family AAA domain-containing protein 2	A	130	Homo sapiens	Mutation(s): 0 Gene Names: ATAD2, L16, PRO2000 EC: 3.6.1.3
UniProt & NIH Common Fund Data Resources
Find proteins for Q6PL18 (Homo sapiens) Explore Q6PL18 Go to UniProtKB: Q6PL18
PHAROS: Q6PL18 GTEx: ENSG00000156802
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q6PL18
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
39U Query on 39U Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A]	E [auth A]	2-amino-7,7-dimethyl-5,6,7,8-tetrahydro-4H-[1,3]thiazolo[5,4-c]azepin-4-one C₉ H₁₃ N₃ O S KRPZAWRISMXVDQ-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain B [auth A] SDF format, chain C [auth A] MOL2 format, chain B [auth A] MOL2 format, chain C [auth A]	B [auth A], C [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain B [auth A] Focus chain C [auth A] Interactions & Density Focus chain B [auth A] Focus chain C [auth A]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A]	D [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
39U	Binding MOAD: 4TZ8	Kd: 5.00e+5 (nM) from 1 assay(s)
39U	BindingDB: 4TZ8	Kd: 5.00e+5 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.15 Å
R-Value Free: 0.231
R-Value Work: 0.198
R-Value Observed: 0.202
Space Group: P 6₅ 2 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 79.942	α = 90
b = 79.942	β = 90
c = 138.259	γ = 120

Software Package:

Software Name	Purpose
PHENIX	refinement
HKL-2000	data scaling
MAR345dtb	data collection
Coot	model building

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2014-10-29

Deposition Author(s):

Funding Organization	Location	Grant Number
National Institutes of Health/National Cancer Institute (NIH/NCI)	United States	DP1OD006933/DP1CA174419

Revision History (Full details and data files)

Version 1.0: 2014-10-29
Type: Initial release
Version 1.1: 2014-12-03
Changes: Database references
Version 1.2: 2015-02-04
Changes: Derived calculations
Version 1.3: 2017-09-06
Changes: Author supporting evidence, Database references, Derived calculations, Other, Source and taxonomy
Version 1.4: 2017-11-22
Changes: Refinement description
Version 1.5: 2019-12-04
Changes: Author supporting evidence
Version 1.6: 2023-09-27
Changes: Data collection, Database references, Refinement description