Fig. 2: Structural basis for CCM binding to human Bmal1(PASB) and induced conformational changes.
From: Pharmacological targeting of BMAL1 modulates circadian and immune pathways
a, Crystal structure of BMAL1(PASB) in complex with CCM. b, Electron density maps in the central cavity of BMAL1(PASB), showing three water molecules in the apo structure (left) and the CCM molecule bound in the complex (right). The R versus S isomers of CCM are shown together. c, CCM binding repositions residues in BMAL1(PASB). d, CCM expands the central pocket volume three-fold. The accessible cavity size (when CCM is removed in the complex and waters are removed in the apo structure) was calculated in PyMol with PvVOL. e, Location of PASB domains of BMAL1 and HIF2α in their respective complexes. Structures used here are from PDB IDs 4F3L, 4H10, 4ZPK and 6E3S. The position of CCM in the complex was added manually based on the BMAL1(PAS) complex structure determined in this study.
