title: Crystal structure of an HD-GYP domain cyclic-di-GMP phosphodiesterase reveals an enzyme with a novel trinuclear catalytic iron centre.
abstract: Bis-(3',5') cyclic di-guanylate (c-di-GMP) is a key bacterial second messenger that is implicated in the regulation of many crucial processes that include biofilm formation, motility and virulence. Cellular levels of c-di-GMP are controlled through synthesis by GGDEF domain diguanylate cyclases and degradation by two classes of phosphodiesterase with EAL or HD-GYP domains. Here, we have determined the structure of an enzymatically active HD-GYP domain protein from Persephonella marina (PmGH) alone, in complex with substrate (c-di-GMP) and final reaction product (GMP). The structures reveal a novel trinuclear iron binding site, which is implicated in catalysis and identify residues involved in recognition of c-di-GMP. This structure completes the picture of all domains involved in c-di-GMP metabolism and reveals that the HD-GYP family splits into two distinct subgroups containing bi- and trinuclear metal centres.
authors.affiliation: Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, UK; Research Complex at Harwell, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0FA, UK.
authors.forename: Dom
authors.initials: D
authors.lastname: Bellini
authors.forename: Delphine L
authors.initials: DL
authors.lastname: Caly
authors.forename: Yvonne
authors.initials: Y
authors.lastname: McCarthy
authors.forename: Mario
authors.initials: M
authors.lastname: Bumann
authors.forename: Shi-Qi
authors.initials: SQ
authors.lastname: An
authors.forename: J Maxwell
authors.initials: JM
authors.lastname: Dow
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ryan
authors.forename: Martin A
authors.initials: MA
authors.lastname: Walsh
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D019143:Evolution, Molecular; D006090:Gram-Negative Bacteria / Q000201:enzymology*; D007501:Iron / Q000378:metabolism*; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D007501:Iron; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP