Inherent Regulation of EAL Domain-catalyzed Hydrolysis of Second Messenger Cyclic Di-GMP

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2014 Jan 24

PMID 24451384

Citations 35

Authors

Amit Sundriyal

Claudia Massa

Dietrich Samoray

Fabian Zehender

Timothy Sharpe

Urs Jenal

Tilman Schirmer

Affiliations

Soon will be listed here.

Abstract

The universal second messenger cyclic di-GMP (cdG) is involved in the regulation of a diverse range of cellular processes in bacteria. The intracellular concentration of the dinucleotide is determined by the opposing actions of diguanylate cyclases and cdG-specific phosphodiesterases (PDEs). Whereas most PDEs have accessory domains that are involved in the regulation of their activity, the regulatory mechanism of this class of enzymes has remained unclear. Here, we use biophysical and functional analyses to show that the isolated EAL domain of a PDE from Escherichia coli (YahA) is in a fast thermodynamic monomer-dimer equilibrium, and that the domain is active only in its dimeric state. Furthermore, our data indicate thermodynamic coupling between substrate binding and EAL dimerization with the dimerization affinity being increased about 100-fold upon substrate binding. Crystal structures of the YahA-EAL domain determined under various conditions (apo, Mg(2+), cdG·Ca(2+) complex) confirm structural coupling between the dimer interface and the catalytic center. The built-in regulatory properties of the EAL domain probably facilitate its modular, functional combination with the diverse repertoire of accessory domains.

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