5LXC

Crystal structure of DYRK2 in complex with EHT 5372 (Compound 1)

PDB DOI: https://doi.org/10.2210/pdb5LXC/pdb

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

Deposited: 2016-09-20 Released: 2016-10-26
Deposition Author(s): Chaikuad, A., von Delft, F., Arrowsmith, C.H., Edwards, A., Bountra, C., Besson, T., Knapp, S., Structural Genomics Consortium (SGC)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.15 Å
R-Value Free: 0.254
R-Value Work: 0.206
R-Value Observed: 0.208

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

An Unusual Binding Model of the Methyl 9-Anilinothiazolo[5,4-f] quinazoline-2-carbimidates (EHT 1610 and EHT 5372) Confers High Selectivity for Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases.

Chaikuad, A., Diharce, J., Schroder, M., Foucourt, A., Leblond, B., Casagrande, A.S., Desire, L., Bonnet, P., Knapp, S., Besson, T.

(2016) J Med Chem 59: 10315-10321

PubMed: 27766861 Search on PubMed
DOI: https://doi.org/10.1021/acs.jmedchem.6b01083
Primary Citation of Related Structures:
5LXC, 5LXD

PubMed Abstract:
Methyl 9-anilinothiazolo[5,4-f]quinazoline-2-carbimidates 1 (EHT 5372) and 2 (EHT 1610) are strong inhibitors of DYRK's family kinases. The crystal structures of the complex revealed a noncanonical binding mode of compounds 1 and 2 in DYRK2, explaining the remarkable selectivity and potency of these inhibitors. The structural data and comparison presented here provide therefore a template for further improvement of this inhibitor class and for the development of novel inhibitors selectively targeting DYRK kinases.

Organizational Affiliation

Target Discovery Institute (TDI), and Structural Genomics Consortium (SGC), University of Oxford , Old Road Campus Research Building, Oxford OX3 7DQ, U.K.

Macromolecule Content

Total Structure Weight: 95.43 kDa
Atom Count: 6,761
Modelled Residue Count: 770
Deposited Residue Count: 816
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Dual specificity tyrosine-phosphorylation-regulated kinase 2	A, B	408	Homo sapiens	Mutation(s): 0 Gene Names: DYRK2 EC: 2.7.12.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q92630 (Homo sapiens) Explore Q92630 Go to UniProtKB: Q92630
PHAROS: Q92630 GTEx: ENSG00000127334
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q92630
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
7AA Query on 7AA Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain L [auth B] MOL2 format, chain C [auth A] MOL2 format, chain L [auth B]	C [auth A], L [auth B]	methyl 9-[(2,4-dichlorophenyl)amino]-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate C₁₇ H₁₁ Cl₂ N₅ O S QSGKPYRFWJINEH-HMMYKYKNSA-N		Interactions Focus chain C [auth A] Focus chain L [auth B] Interactions & Density Focus chain C [auth A] Focus chain L [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain E [auth A] 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 M [auth B] SDF format, chain N [auth B] SDF format, chain O [auth B] SDF format, chain D [auth A] MOL2 format, chain E [auth A] 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 M [auth B] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] MOL2 format, chain D [auth A]	D [auth A] E [auth A] F [auth A] G [auth A] H [auth A] D [auth A], E [auth A], F [auth A], G [auth A], H [auth A], I [auth A], J [auth A], K [auth A], M [auth B], N [auth B], O [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] 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 M [auth B] Focus chain N [auth B] Focus chain O [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] 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 M [auth B] Focus chain N [auth B] Focus chain O [auth B]