5Z7C

crystal structure of cyclic GMP-AMP specifc phosphodiesterases in V.cholerae (V-cGAP3)

Summary for 5Z7C

• Entry DOI: 10.2210/pdb5z7c/pdb
• Descriptor: 3'3'-cGAMP-specific phosphodiesterase 3 (2 entities in total)
• Functional Keywords: cyclic dinucleotides, phosphodiesterase., metal binding protein
• Biological source: Vibrio cholerae O1 biovar El Tor str. N16961
• Total number of polymer chains: 1
• Total formula weight: 51564.65

Authors

Deng, M.J.,Ye, Z.Y.,Su, X.D. (deposition date: 2018-01-28, release date: 2019-01-02, Last modification date: 2024-10-23)

Primary citation

Deng, M.J.,Tao, J.,E, C.,Ye, Z.Y.,Jiang, Z.,Yu, J.,Su, X.D.
Novel Mechanism for Cyclic Dinucleotide Degradation Revealed by Structural Studies of Vibrio Phosphodiesterase V-cGAP3.
J. Mol. Biol., 430:5080-5093, 2018

PubMed Abstract: 3'3'-cyclic GMP-AMP (3'3'-cGAMP) belongs to a family of the bacterial secondary messenger cyclic dinucleotides. It was first discovered in the Vibrio cholerae seventh pandemic strains and is involved in efficient intestinal colonization and chemotaxis regulation. Phosphodiesterases (PDEs) that degrade 3'3'-cGAMP play important regulatory roles in the relevant signaling pathways, and a previous study has identified three PDEs in V. cholerae, namely, V-cGAP1, V-cGAP2, and V-cGAP3, functioning in 3'3'-cGAMP degradation. We report the crystal structure, biochemical, and structural analyses of V-cGAP3, providing a foundation for understanding the mechanism of 3'3'-cGAMP degradation and regulation in general. Our crystal and molecular dynamic (MD)-simulated structures revealed that V-cGAP3 contains tandem HD-GYP domains within its N- and C-terminal domains, with similar three-dimensional topologies despite their low-sequence identity. Biochemical and structural analyses showed that the N-terminal domain plays a mechanism of positive regulation for the catalytic C-terminal domain. We also demonstrated that the other homologous Vibrio PDEs, V-cGAP1/2, likely function via a similar mechanism.

PubMed: 30365951
DOI: 10.1016/j.jmb.2018.10.010

Experimental method

X-RAY DIFFRACTION (2.76 Å)