Role of DHH superfamily proteins in nucleic acids metabolism and stress tolerance in prokaryotes and eukaryotes

A pGpG-specific phosphodiesterase regulates cyclic di-GMP signaling in Vibrio cholerae

“…Mutations at His68 and Asp121 completely abolished enzymatic activity, indicating that the coordination with divalent cation is essential for its activity as other DHH/DHHA1 family PDEs ( Fig. S3 ) ( 21 ). Mutations at the two aspartate residues, Asp13 and Asp67, also abolished the enzymatic activity, implicating their importance in stabilizing the positions of the Mn 2+ -coordinating residues ( Fig.…”

“…Therefore, it can be classified as a DHH/DHHA1 family enzyme. The DHH/DHHA1 family enzymes are involved in the hydrolysis of oligonucleotides in various bacterial species (21), such as the Thermotoga J o u r n a l P r e -p r o o f maritima PDE TM1595, which hydrolyzes various linear dinucleotides (22); PDE YybT, which hydrolyzes cyclic dinucleotides (c-di-GMP and c-di-AMP) (23); the 3ʹ-phosphoadenosine 5ʹphosphate (pAp) phosphatase YtqI (24) in Bacillus subtilis; the single-stranded DNA (ssDNA) exonuclease RecJ, which is highly conserved in most bacterial and archaea (25). Thus, we assumed that VCA0593 might exhibit nucleotide-hydrolyzing activity.…”

Genome-wide functional analysis of phosphatases in the pathogenic fungus Cryptococcus neoformans

“…Here we found that the following pathogenicity-related phosphatases are also involved in BBB crossing of C. neoformans : Xpp1, Sit4, Ssu72, Siw14, and Gda1. In S. cerevisiae , Ppx1 (the orthologue of Xpp1) is a metal-dependent cytosolic expolyphosphatase and generates inorganic phosphate by cleaving polyphosphate that serves as a major phosphate reservoir and is required for long-term cell survival, gene regulation, cell motility, and stress responses 83 . The functions of Sit4 and Ssu72 are likely related to the target of rapamycin (TOR) pathway involved in nutrient-sensing.…”

A Membrane-Associated DHH-DHHA1 Nuclease Degrades Type III CRISPR Second Messenger

“…The data are consistent with the activity of the 7# fraction and characterized DHH-DHHA1 family nucleases. Depending on different subgroups, the substrates of DHH-DHHA1 family proteins vary from cyclic di-nucleotides, nanoRNA to ssDNA (Srivastav et al, 2019), suggesting that this family of proteins, in contrast to ring nuclease, has a board substrate spectrum. To preliminarily investigate the substrate spectrum of SiRe_0244, we analyzed whether SiRe_0244 degrades single-stranded RNA (ssRNA), double-stranded RNA (dsRNA), singlestranded DNA (ssDNA), and double-stranded DNA (dsDNA).…”