| First Author | Kato K | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4424 |
| PubMed ID | 30356045 | Mgi Jnum | J:273505 |
| Mgi Id | MGI:6294158 | Doi | 10.1038/s41467-018-06922-7 |
| Citation | Kato K, et al. (2018) Structural insights into cGAMP degradation by Ecto-nucleotide pyrophosphatase phosphodiesterase 1. Nat Commun 9(1):4424 |
| abstractText | ENPP1 (Ecto-nucleotide pyrophosphatase phosphodiesterase 1), a type II transmembrane glycoprotein, hydrolyzes ATP to produce AMP and diphosphate, thereby inhibiting bone mineralization. A recent study showed that ENPP1 also preferentially hydrolyzes 2'3'-cGAMP (cyclic GMP-AMP) but not its linkage isomer 3'3'-cGAMP, and negatively regulates the cGAS-STING pathway in the innate immune system. Here, we present the high-resolution crystal structures of ENPP1 in complex with 3'3'-cGAMP and the reaction intermediate pA(3',5')pG. The structures revealed that the adenine and guanine bases of the dinucleotides are recognized by nucleotide- and guanine-pockets, respectively. Furthermore, the structures indicate that 2'3'-cGAMP, but not 3'3'-cGAMP, binds to the active site in a conformation suitable for catalysis, thereby explaining the specific degradation of 2'3'-cGAMP by ENPP1. Our findings provide insights into how ENPP1 hydrolyzes both ATP and cGAMP to participate in the two distinct biological processes. |
