PuSH - Publikationsserver des Helmholtz Zentrums München: Structural perspective on the design of selective DYRK1B inhibitors.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Grygier, P.* ; Pustelny, K.* ; Cardoso Micu Menezes, F.M. ; Jemiola-Rzeminska, M.* ; Suder, P.* ; Dubin, G.* ; Czarna, A.*

Structural perspective on the design of selective DYRK1B inhibitors.

Int. J. Biol. Macromol. 330:148124 (2025)

Verlagsversion

Forschungsdaten

DOI

PMC

	Open Access Hybrid

Abstract
Metriken
Zusatzinfos

Dual-specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B) has recently emerged as a critical therapeutic target in oncology and non-alcoholic fatty liver disease. As a kinase, DYRK1B plays key roles in regulating cellular survival pathways; however, the lack of structural information has impeded the development of selective inhibitors. In this study, we implemented multi-method framework: recombinant expression and stability profiling, cellular target engagement, enzyme inhibition, biophysical thermodynamics, cell-based pathway readout, X-ray crystallography, quantum-mechanical and molecular-dynamics analyses. We report the crystal structure of DYRK1B in complex with the small-molecule inhibitor AZ191. For comparative purposes, we also present the structure of the closely related kinase, DYRK1A, bound to the same ligand. While a structural overlay of the two kinase domains reveals overall negligible differences, detailed inspection highlights distinct features within the hinge-binding region of DYRK1B that are pivotal for achieving kinase selectivity. Moreover, detailed evaluation of the active site architecture reveals a notable difference in the accessibility of the catalytic lysine residue between DYRK1B and DYRK1A, suggesting potential strategies to distinguish selective binders. Overall, these findings provide important macromolecular insights into the DYRK1B structure and offer a structural framework to guide medicinal chemistry efforts towards improved inhibitor selectivity with minimized off-target activity.

Impact Factor

Scopus SNIP

Altmetric

8.500

0.000