Structural and Chemical Biology Approaches Reveal Isoform-Selective Mechanisms of Ligand Interactions in Mammalian Cryptochromes.

ABSTRACT: Cryptochromes (CRYs) are core components of the circadian feedback loop in mammals, which regulates circadian rhythmicity in a variety of physiological processes including sleep-wake cycles and metabolism. Dysfunction of CRY1 and CRY2 isoforms has been associated with a host of diseases, such as sleep phase disorder and metabolic diseases. Accumulating evidence for distinct roles of CRY1 and CRY2 has highlighted the need for CRY isoform-selective regulation; however, highly conserved sequences in CRY ligand-binding sites have hindered the design of isoform-selective compounds. Chemical biology approaches have been identifying small-molecule modulators of CRY proteins, which act in isoform-non-selective and also isoform-selective manners. In this review, we describe advances in our understa

SUBMITTER: Miller S 

PROVIDER: S-EPMC8831909 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature