SARM1, an Enzyme Involved in Axon Degeneration, Catalyzes Multiple Activities through a Ternary Complex Mechanism.

ABSTRACT: Sterile alpha and toll/interleukin receptor (TIR) motif containing protein 1 (SARM1) is an NAD⁺ hydrolase and cyclase involved in axonal degeneration. In addition to NAD⁺ hydrolysis and cyclization, SARM1 catalyzes a base exchange reaction between nicotinic acid (NA) and NADP⁺ to generate NAADP, which is a potent calcium signaling molecule. Herein, we describe efforts to characterize the hydrolysis, cyclization, and base exchange activities of TIR-1, the Caenorhabditis elegans ortholog of SARM1; TIR-1 also catalyzes NAD(P)⁺ hydrolysis and/or cyclization and regulates axonal degeneration in worms. We show that the catalytic domain of TIR-1 undergoes a liquid-to-solid phase transition that regulates not only the hydrolysis and cyclization re

SUBMITTER: Icso JD 

PROVIDER: S-EPMC10795796 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature