Structural and Mechanistic Regulation of the Pro-degenerative NAD Hydrolase SARM1

Matthew Bratkowski, Tian Xie, Desiree A. Thayer, Shradha Lad, Prakhyat Mathur, Yu San Yang, Gregory Danko, Thomas C. Burdett, Jean Danao, Aaron Cantor, Jennifer A. Kozak, Sean P. Brown, Xiaochen Bai, Shilpa Sambashivan

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Bratkowski et al. describe cryo-EM structures of autoinhibited and active SARM1, an axon-enriched, injury-activated NADase. Structure-function studies elucidate the mode of autoinhibition and SARM1 activity regulation. The authors provide mechanistic insight into SARM1’s regulation by the local metabolic environment, laying the foundation for future SARM1-based therapies to treat neurological diseases.

Original languageEnglish (US)
Article number107999
JournalCell Reports
Issue number5
StatePublished - Aug 4 2020


  • NAD hydrolase
  • NAM
  • NMN
  • SARM1
  • autoinhibition
  • axon
  • axonopathies
  • cryo-EM

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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