Function
SARM1 or NAD(+) hydrolase or sterile alpha and TIR motif-containing protein 1 or NADase is a NAD-cleaving enzyme whose activation triggers axon destruction. SARM1 is a metabolic sensor responding to an increased NMN/NAD+ ratio by cleaving residual NAD+ and inducing axonal demise[1]. SARM1-induced axon destruction can be counteracted by increased NAD+ synthesis[2].
Disease
SARM1 mutations were found in ALS patients[3].
Structural highlights
The 3D structure of SARM1 shows the octamer structure with outer ring dimension of 200A, inner ring of 45A and thickness of 60A[4].. The 3 domains of SARM1 are ARM, SAM and TIR. The interaction of the ARM and TIR domains cause the autoinhibition of SARM1. NAD(+) binding pocket is at the concave side of the ARM domain.
3D structures of SARM1
SARM1 3D structures