4D2S

Human TTK in complex with a Dyrk1B inhibitor

PDB DOI: https://doi.org/10.2210/pdb4D2S/pdb

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

Deposited: 2014-05-12 Released: 2015-04-22
Deposition Author(s): Debreczeni, J.E., Kettle, J.G., Ballard, P., Bardelle, C., Butterworth, S., Colclough, N., Critchlow, S.E., Fairley, G., Fillery, S., Graham, M.A., Goodwin, L., Guichard, S., Hudson, K., Mahmood, A., Vincent, J., Ward, R.A., Whittaker, D.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.50 Å
R-Value Free: 0.221
R-Value Work: 0.179
R-Value Observed: 0.181

wwPDB Validation 3D Report Full Report

This is version 1.1 of the entry. See complete history.

Literature

Discovery and Optimization of a Novel Series of Dyrk1B Kinase Inhibitors to Explore a Mek Resistance Hypothesis.

Kettle, J.G., Ballard, P., Bardelle, C., Cockerill, M., Colclough, N., Critchlow, S.E., Debreczeni, J.E., Fairley, G., Fillery, S., Graham, M.A., Goodwin, L., Guichard, S., Hudson, K., Ward, R.A., Whittaker, D.

(2015) J Med Chem 58: 2834

PubMed: 25738750 Search on PubMed
DOI: https://doi.org/10.1021/acs.jmedchem.5b00098
Primary Citation of Related Structures:
4D2R, 4D2S

PubMed Abstract:
Potent and selective inhibitors of Dyrk1B kinase were developed to explore the hypothesis, based on siRNA studies, that Dyrk1B may be a resistance mechanism in cells undergoing a stress response.

Organizational Affiliation

Oncology iMed, AstraZeneca, Alderley Park, Macclesfield, SK10 4TG, United Kingdom.

Macromolecule Content

Total Structure Weight: 33.09 kDa
Atom Count: 1,937
Modelled Residue Count: 249
Deposited Residue Count: 284
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
DUAL SPECIFICITY PROTEIN KINASE TTK	A	284	Homo sapiens	Mutation(s): 0 EC: 2.7.12.1
UniProt & NIH Common Fund Data Resources
Find proteins for P33981 (Homo sapiens) Explore P33981 Go to UniProtKB: P33981
PHAROS: P33981 GTEx: ENSG00000112742
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P33981
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
DYK Query on DYK Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	N-{2-methoxy-4-[(1-methylpiperidin-4-yl)oxy]phenyl}-4-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyrimidin-2-amine C₂₄ H₂₆ N₆ O₂ FTZQWKAIKYEWPM-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
DYK	BindingDB: 4D2S	IC50: 20 (nM) from 1 assay(s)
DYK	Binding MOAD: 4D2S	IC50: 20 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.50 Å
R-Value Free: 0.221
R-Value Work: 0.179
R-Value Observed: 0.181
Space Group: C 2 2 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 108.013	α = 90
b = 113.352	β = 90
c = 71.038	γ = 90

Software Package:

Software Name	Purpose
BUSTER	refinement
MOSFLM	data reduction
SCALA	data scaling
AMoRE	phasing

Structure Validation

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Entry History

Deposition Data

Released Date: 2015-04-22

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2015-04-22
Type: Initial release
Version 1.1: 2019-10-23
Changes: Data collection, Experimental preparation, Other, Structure summary

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Help and Resources

4D2S

Human TTK in complex with a Dyrk1B inhibitor

Discovery and Optimization of a Novel Series of Dyrk1B Kinase Inhibitors to Explore a Mek Resistance Hypothesis.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

Expand

Experimental Data

Structure Validation

Deposition Data

Revision History (Full details and data files)