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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.

SUBMITTER: Miner KD

PROVIDER: S-EPMC3769106 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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An HD-GYP cyclic di-guanosine monophosphate phosphodiesterase with a non-heme diiron-carboxylate active site.

Miner Kyle D KD Klose Karl E KE Kurtz Donald M DM

Biochemistry 20130729 32

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 H ...[more]

PMID: 23883166

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