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The Heme-Based Oxygen-Sensor Phosphodiesterase Ec DOS (DosP): Structure-Function Relationships.

Shimizu T - Biosensors (Basel) (2013)

Bottom Line: Notably, its activity is markedly enhanced by O2 binding to the heme Fe(II) complex in the PAS sensor domain.X-ray crystal structures and spectroscopic and catalytic characterization of the wild-type and mutant proteins have provided important structural and functional clues to understanding the molecular mechanism of intramolecular catalytic regulation by O2 binding.This review summarizes the intriguing findings that have obtained for Ec DOS.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Shantou University Medical College, Shantou 515041, China. shimizu@tagen.tohoku.ac.jp.

ABSTRACT
Escherichia coli Direct Oxygen Sensor (Ec DOS, also known as Ec DosP) is a heme-based O2-sensing phosphodiesterase from Escherichia coli that catalyzes the conversion of cyclic-di-GMP to linear di-GMP. Cyclic-di-GMP is an important second messenger in bacteria, highlighting the importance of understanding structure-function relationships of Ec DOS. Ec DOS is composed of an N-terminal heme-bound O2-sensing PAS domain and a C-terminal phosphodiesterase catalytic domain. Notably, its activity is markedly enhanced by O2 binding to the heme Fe(II) complex in the PAS sensor domain. X-ray crystal structures and spectroscopic and catalytic characterization of the wild-type and mutant proteins have provided important structural and functional clues to understanding the molecular mechanism of intramolecular catalytic regulation by O2 binding. This review summarizes the intriguing findings that have obtained for Ec DOS.

No MeSH data available.


Related in: MedlinePlus

Mn2+ facilitates PDE catalytic activity toward c-di-GMP, but the catalytic mechanism is different from that of Mg2+. In the presence of Mn2+, full-length Ec DOS containing a heme Fe(III) complex exhibits fully competent PDE functions, catalyzing the two-step conversion of c-di-GMP all the way to GMP via l-di-GMP [35]. The first reaction from c-di-GMP to l-di-GMP is much faster with Mn2+ than with Mg2+, and the second reaction (cleaving l-di-GMP to form GMP) does not occur in the presence of Mg2+. Adapted from [35].
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biosensors-03-00211-f009: Mn2+ facilitates PDE catalytic activity toward c-di-GMP, but the catalytic mechanism is different from that of Mg2+. In the presence of Mn2+, full-length Ec DOS containing a heme Fe(III) complex exhibits fully competent PDE functions, catalyzing the two-step conversion of c-di-GMP all the way to GMP via l-di-GMP [35]. The first reaction from c-di-GMP to l-di-GMP is much faster with Mn2+ than with Mg2+, and the second reaction (cleaving l-di-GMP to form GMP) does not occur in the presence of Mg2+. Adapted from [35].

Mentions: Mn2+, like Mg2+, mediates phosphorylation, dephosphorylation, and PDE reactions that facilitate catalytic activity [34]. To understand how Mn2+ behaves in the heme-based oxygen-sensor PDE, Ec DOS, the catalysis of c-di-GMP in the presence of Mn2+ instead of Mg2+ was examined [35]. The study showed that, in the presence of Mn2+, Ec DOS-heme Fe(III) mediates the two-step hydrolysis of c-di-GMP into GMP via the linear-di-GMP intermediate (Figure 9). By contrast, in the presence of Mg2+, the first linearization reaction of c-di-GMP is much slower than that in the presence of Mn2+, and the second reaction to form GMP is not observed for Ec DOS-heme Fe(III) [25,26]. Thus, Ec DOS-heme Fe(III), which is inactive in the presence of Mg2+, exhibits PDE activity in the presence of Mn2+, implying that the Mn2+ binds to the catalytic domain and that Mn2+-bound form of Ec DOS without exogenous ligands mimics the Mg2+-bound form, which is only induced upon O2 (or NO/CO) binding to Ec DOS-heme Fe(II). It has been speculated that Mn2+ may be situated or coordinated at an active-site position that, even in Ec DOS-heme Fe(III), is suitable for promoting optimal catalytic activity comparable to that observed for the heme Fe(II)-O2 form with Mg2+. Thus, one plausible explanation for the gas-sensing function of Ec DOS is that O2 (or NO/CO) binding enhances Mg2+ affinity for the active site and/or creates a Mg2+ coordination structure that is optimal for efficient PDE catalysis.


The Heme-Based Oxygen-Sensor Phosphodiesterase Ec DOS (DosP): Structure-Function Relationships.

Shimizu T - Biosensors (Basel) (2013)

Mn2+ facilitates PDE catalytic activity toward c-di-GMP, but the catalytic mechanism is different from that of Mg2+. In the presence of Mn2+, full-length Ec DOS containing a heme Fe(III) complex exhibits fully competent PDE functions, catalyzing the two-step conversion of c-di-GMP all the way to GMP via l-di-GMP [35]. The first reaction from c-di-GMP to l-di-GMP is much faster with Mn2+ than with Mg2+, and the second reaction (cleaving l-di-GMP to form GMP) does not occur in the presence of Mg2+. Adapted from [35].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263535&req=5

biosensors-03-00211-f009: Mn2+ facilitates PDE catalytic activity toward c-di-GMP, but the catalytic mechanism is different from that of Mg2+. In the presence of Mn2+, full-length Ec DOS containing a heme Fe(III) complex exhibits fully competent PDE functions, catalyzing the two-step conversion of c-di-GMP all the way to GMP via l-di-GMP [35]. The first reaction from c-di-GMP to l-di-GMP is much faster with Mn2+ than with Mg2+, and the second reaction (cleaving l-di-GMP to form GMP) does not occur in the presence of Mg2+. Adapted from [35].
Mentions: Mn2+, like Mg2+, mediates phosphorylation, dephosphorylation, and PDE reactions that facilitate catalytic activity [34]. To understand how Mn2+ behaves in the heme-based oxygen-sensor PDE, Ec DOS, the catalysis of c-di-GMP in the presence of Mn2+ instead of Mg2+ was examined [35]. The study showed that, in the presence of Mn2+, Ec DOS-heme Fe(III) mediates the two-step hydrolysis of c-di-GMP into GMP via the linear-di-GMP intermediate (Figure 9). By contrast, in the presence of Mg2+, the first linearization reaction of c-di-GMP is much slower than that in the presence of Mn2+, and the second reaction to form GMP is not observed for Ec DOS-heme Fe(III) [25,26]. Thus, Ec DOS-heme Fe(III), which is inactive in the presence of Mg2+, exhibits PDE activity in the presence of Mn2+, implying that the Mn2+ binds to the catalytic domain and that Mn2+-bound form of Ec DOS without exogenous ligands mimics the Mg2+-bound form, which is only induced upon O2 (or NO/CO) binding to Ec DOS-heme Fe(II). It has been speculated that Mn2+ may be situated or coordinated at an active-site position that, even in Ec DOS-heme Fe(III), is suitable for promoting optimal catalytic activity comparable to that observed for the heme Fe(II)-O2 form with Mg2+. Thus, one plausible explanation for the gas-sensing function of Ec DOS is that O2 (or NO/CO) binding enhances Mg2+ affinity for the active site and/or creates a Mg2+ coordination structure that is optimal for efficient PDE catalysis.

Bottom Line: Notably, its activity is markedly enhanced by O2 binding to the heme Fe(II) complex in the PAS sensor domain.X-ray crystal structures and spectroscopic and catalytic characterization of the wild-type and mutant proteins have provided important structural and functional clues to understanding the molecular mechanism of intramolecular catalytic regulation by O2 binding.This review summarizes the intriguing findings that have obtained for Ec DOS.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Shantou University Medical College, Shantou 515041, China. shimizu@tagen.tohoku.ac.jp.

ABSTRACT
Escherichia coli Direct Oxygen Sensor (Ec DOS, also known as Ec DosP) is a heme-based O2-sensing phosphodiesterase from Escherichia coli that catalyzes the conversion of cyclic-di-GMP to linear di-GMP. Cyclic-di-GMP is an important second messenger in bacteria, highlighting the importance of understanding structure-function relationships of Ec DOS. Ec DOS is composed of an N-terminal heme-bound O2-sensing PAS domain and a C-terminal phosphodiesterase catalytic domain. Notably, its activity is markedly enhanced by O2 binding to the heme Fe(II) complex in the PAS sensor domain. X-ray crystal structures and spectroscopic and catalytic characterization of the wild-type and mutant proteins have provided important structural and functional clues to understanding the molecular mechanism of intramolecular catalytic regulation by O2 binding. This review summarizes the intriguing findings that have obtained for Ec DOS.

No MeSH data available.


Related in: MedlinePlus