Conservation of structure, function and inhibitor binding in UNC-51-like kinase 1 and 2 (ULK1/2).

ABSTRACT: Autophagy is essential for cellular homeostasis and when deregulated this survival mechanism has been associated with disease development. Inhibition of autophagy initiation by inhibiting the kinase ULK1 (Unc-51-like autophagy activating kinase 1) has been proposed as a potential cancer therapy. While inhibitors and crystal structures of ULK1 have been reported, little is known about the other closely related kinase ULK2 (Unc-51-like autophagy activating kinase 2). Here, we present the crystal structure of ULK2 in complex with ATP competitive inhibitors. Surprisingly, the ULK2 structure revealed a dimeric assembly reminiscent of dimeric arrangements of auto-activating kinases suggesting a role for this association in ULK activation. Screening of a kinase focused library of pre-clinical and

SUBMITTER: Chaikuad A 

PROVIDER: S-EPMC10275411 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature