biostudies-literatureHeo KMinistry of Science, ICT and Future PlanningKorea Ministry of Science and ICTNational Research Foundation of Korea101626https://www.ebi.ac.uk/biostudies/studies/S-EPMC8861645biostudies-literatureUnknown298(3)The bacterial second messenger bis-(3'-5')-cyclic diguanylate monophosphate (c-di-GMP) controls various cellular processes, including motility, toxin production, and biofilm formation. c-di-GMP is enzymatically synthesized by GGDEF domain-containing diguanylate cyclases and degraded by HD-GYP domain-containing phosphodiesterases (PDEs) to 2 GMP or by EAL domain-containing PDE-As to 5'-phosphoguanylyl-(3',5')-guanosine (pGpG). Since excess pGpG feedback inhibits PDE-A activity and thereby can lead to the uncontrolled accumulation of c-di-GMP, a PDE that degrades pGpG to 2 GMP (PDE-B) has been presumed to exist. To date, the only enzyme known to hydrolyze pGpG is oligoribonuclease Orn, which degrades all kinds of oligoribonucleotides. Here, we identified a pGpG-specific PDE, which we named PThe Journal of biological chemistryA pGpG-specific phosphodiesterase regulates cyclic di-GMP signaling in Vibrio cholerae.PMC8861645NRF-2019R1A2C2004143NRF-2018R1A5A1025077Kwon SSeok CJang YLee JHeo KLee JWHa NCSeok YJfalseA pGpG-specific phosphodiesterase regulates cyclic di-GMP signaling in Vibrio cholerae.The bacterial second messenger bis-(3'-5')-cyclic diguanylate monophosphate (c-di-GMP) controls various cellular processes, including motility, toxin production, and biofilm formation. c-di-GMP is enzymatically synthesized by GGDEF domain-containing diguanylate cyclases and degraded by HD-GYP domain-containing phosphodiesterases (PDEs) to 2 GMP or by EAL domain-containing PDE-As to 5'-phosphoguanylyl-(3',5')-guanosine (pGpG). Since excess pGpG feedback inhibits PDE-A activity and thereby can lead to the uncontrolled accumulation of c-di-GMP, a PDE that degrades pGpG to 2 GMP (PDE-B) has been presumed to exist. To date, the only enzyme known to hydrolyze pGpG is oligoribonuclease Orn, which degrades all kinds of oligoribonucleotides. Here, we identified a pGpG-specific PDE, which we named P2022-01-01T00:00:00Z2022 Mar2025-04-04T20:50:44.133Z2025-04-04T20:50:44.133ZS-EPMC88616453507442510.1016/j.jbc.2022.101626