title: An HD-GYP cyclic di-guanosine monophosphate phosphodiesterase with a non-heme diiron-carboxylate active site.
abstract: The intracellular level of the ubiquitous bacterial secondary messenger, cyclic di-(3',5')-guanosine monophosphate (c-di-GMP), represents a balance between its biosynthesis and degradation, the latter via specific phosphodiesterases (PDEs). One class of c-di-GMP PDEs contains a characteristic HD-GYP domain. Here we report that an HD-GYP PDE from Vibrio cholerae contains a non-heme diiron-carboxylate active site, and that only the reduced form is active. An engineered D-to-A substitution in the HD dyad caused loss of c-di-GMP PDE activity and of two iron atoms. This report constitutes the first demonstration that a non-heme diiron-carboxylate active site can catalyze the c-di-GMP PDE reaction and that this activity can be redox regulated in the HD-GYP class.
authors.affiliation: Department of Chemistry, University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Miner
authors.forename: Karl E
authors.initials: KE
authors.lastname: Klose
authors.forename: Donald M
authors.initials: DM
authors.lastname: Kurtz
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000737:chemistry; D006418:Heme / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D006418:Heme; C062025:bis(3',5')-cyclic diguanylic acid; D007501:Iron; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP