Sandbox GGC1

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Function

SARM1 is a protein that contains SAM and TIR domains. SARM1 is involved in the cleavage of NAD+. The SAM domains form an octamer and play a part in axon degeneration by contributing to the enzymatic activity of TIR, which will cleave NAD+.

Disease

The SAM domains are involved in Wallerian degeneration. In Wallerian degeneration, axons are degenerated following damage. This nerve damage can lead to neuropathic diseases. SARM1 causes cell death in plants also by cleaving NAD+.

Structural highlights

The SAM domains need to form an octamer for SARM1 to be able to cleave NAD+. Five were found to be important for this to occur: Leu 442, Ile 461, Leu 514, Leu 531, and Val 533. These amino acids are found in that make up the octamer. were changed to arginine or aspartate, then NAD+ would no longer be able to be cleaved.

Relevance

If the five amino acids in the SAM domains that help form the octamer are changed to arginine or asparagine, then it may be possible to inhibit the function of SARM1 and thus stop or slow down neuropathies.