Structural basis for ITP-selective hydrolysis by a CRISPR-associated Nudix hydrolase.

CRISPR-associated Nudix hydrolase from Limisphaera ngatamarikiensis specifically hydrolyzes ITP, with structural insights revealing key interactions for nucleotide recognition.

• Why it matters: Maintaining nucleotide quality is essential for cell health, especially during antiviral responses where noncanonical nucleotides like ITP can accumulate and cause toxicity. Understanding these mechanisms fills a gap in knowledge about bacterial self-protection within CRISPR systems.
• What they did: Researchers determined crystal structures of Lng NH in apo and ITP-bound forms using catalytic mutants, and validated interactions through site-directed mutagenesis, revealing how the enzyme recognizes ITP.
• The result: Findings suggest that CRISPR-associated Nudix hydrolases serve as local self-protection modules, providing a structural basis for nucleotide sanitization that limits toxicity during immune responses.