Reaction participants Show >> << Hide
- Name help_outline 5'-pGpA(2'-5') Identifier CHEBI:228270 Charge -3 Formula C20H23N10O14P2 InChIKeyhelp_outline GMLXOOYDDUZWOK-INFSMZHSSA-K SMILEShelp_outline P(OC[C@H]1O[C@H]([C@@H]([C@@H]1O)OP(OC[C@H]2O[C@H]([C@@H]([C@@H]2O)O)N3C=NC=4C(=NC=NC43)N)(=O)[O-])N5C=NC=6C(NC(=NC65)N)=O)(=O)([O-])[O-] 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,204 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 5'-GpA(2'-5') Identifier CHEBI:228271 Charge -1 Formula C20H24N10O11P InChIKeyhelp_outline ZLNKIMYMVZHDPX-INFSMZHSSA-M SMILEShelp_outline O(C[C@H]1O[C@H]([C@@H]([C@@H]1O)O)N2C=NC=3C(=NC=NC32)N)P(=O)(O[C@H]4[C@@H](O[C@@H]([C@H]4O)CO)N5C=NC=6C(NC(=NC65)N)=O)[O-] 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline phosphate Identifier CHEBI:43474 Charge -2 Formula HO4P InChIKeyhelp_outline NBIIXXVUZAFLBC-UHFFFAOYSA-L SMILEShelp_outline OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 992 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:78343 | RHEA:78344 | RHEA:78345 | RHEA:78346 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensing.
Hou Y., Wang Z., Liu P., Wei X., Zhang Z., Fan S., Zhang L., Han F., Song Y., Chu L., Zhang C.
Lipid metabolism has been associated with the cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) stimulator of interferon genes (STING) DNA-sensing pathway, but our understanding of how these signals are integrated into a cohesive immunometabolic program is lacking. Here, we have identified ... >> More
Lipid metabolism has been associated with the cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) stimulator of interferon genes (STING) DNA-sensing pathway, but our understanding of how these signals are integrated into a cohesive immunometabolic program is lacking. Here, we have identified liver X receptor (LXR) agonists as potent inhibitors of STING signaling. We show that stimulation of lipid metabolism by LXR agonists specifically suppressed cyclic GMP-AMP (cGAMP)-STING signaling. Moreover, we developed cyclic dinucleotide-conjugated beads to biochemically isolate host effectors for cGAMP inhibition, and we found that LXR ligands stimulated the expression of sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A), which is a 2'3'-cGAMP-degrading enzyme. Results of crystal structures suggest that cGAMP analog induces dimerization of SMPDL3A, and the dimerization is critical for cGAMP degradation. Additionally, we have provided evidence that SMPDL3A cleaves cGAMP to restrict STING signaling in cell culture and mouse models. Our results reveal SMPDL3A as a cGAMP-specific nuclease and demonstrate a mechanism for how LXR-associated lipid metabolism modulates STING-mediated innate immunity. << Less
Immunity 56:2492-2507(2023) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.