Finally! The structural secrets of a HD ‐ GYP phosphodiesterase revealed

Summary 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 M olecular M icrobiology , B ellini 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 Pm GH , a catalytically active family member from the thermophilic bacterium P ersephonella 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.