High-resolution structure of the catalytic region of MICAL (molecule interacting with CasL), a multidomain flavoenzyme-signaling molecule.

摘要: Semaphorins are extracellular cell guidance cues that govern cytoskeletal dynamics during neuronal and vascular development. MICAL (molecule interacting with CasL) is a multidomain cytosolic protein putative flavoprotein monooxygenase (MO) region required for semaphorin-plexin repulsive axon guidance. Here, we report the 1.45-A resolution crystal structure of FAD-containing MO domain mouse MICAL-1 (residues 1-489). The topology most closely resembles NADPH-dependent flavoenzyme p-hydroxybenzoate hydroxylase (PHBH). Comparison structures before after reaction NADPH reveals that, as in PHBH, flavin ring can switch between two discrete positions. In contrast other MOs, this conformational coupled opening channel to active site, suggestive substrate. support hypothesis, distinctive structural features highlight protein-binding sites suitable proximity site entrance. unusual juxtaposition N-terminal (hydroxylase) activity characteristics multiprotein-binding scaffold exhibited by C-terminal portion MICALs represents unique combination functionality mediate signaling.