Finally! The structural secrets of a HD-GYP phosphodiesterase revealed.
The major sessility-motility lifestyle change and additional fundamental aspects of bacterial physiology, behaviour and morphology are regulated by the secondary messenger cyclic di-GMP (c-di-GMP). Although the c-di-GMP metabolizing enzymes and many receptors have been readily characterized upon discovery, the HD-GYP domain c-di-GMP phosphodiesterase family remained underinvestigated. In this issue of Molecular Microbiology, Bellini et al. provide an important step towards functional and structural characterization of the previously neglected HD-GYP domain family by resolving the crystal structure of PmGH, a catalytically active family member from the thermophilic bacterium Persephonella marina. The crystal structure revealed a novel tri-nuclear catalytic iron centre involved in c-di-GMP binding and catalysis and provides the structural basis to subsequently characterize in detail the catalytic mechanism of hydrolysis of c-di-GMP to GMP by HD-GYP domains.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Edvard
E
Wigren
Zhao-Xun
ZX
Liang
Ute
U
Römling
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000201:enzymology*; D007501:Iron / Q000378:metabolism*
D001426:Bacterial Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D007501:Iron; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP