4LJ3

Crystal structure of the EAL domain of c-di-GMP specific phosphodiesterase YahA in complex with substrate c-di-GMP and Ca++

Summary for 4LJ3

• Entry DOI: 10.2210/pdb4lj3/pdb
• Related: 4KIE 4lyk
• Descriptor: Cyclic di-GMP phosphodiesterase YahA, 9,9'-[(2R,3R,3aS,5S,7aR,9R,10R,10aS,12S,14aR)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-2,9-diyl]bis(2-amino-1,9-dihydro-6H-purin-6-one), CALCIUM ION, ... (6 entities in total)
• Functional Keywords: pgpg, phosphodiesterase, tim-barrel, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 64101.03

Authors

Sundriyal, A.,Schirmer, T. (deposition date: 2013-07-04, release date: 2014-01-29, Last modification date: 2023-09-20)

Primary citation

Sundriyal, A.,Massa, C.,Samoray, D.,Zehender, F.,Sharpe, T.,Jenal, U.,Schirmer, T.
Inherent Regulation of EAL Domain-catalyzed Hydrolysis of Second Messenger Cyclic di-GMP.
J.Biol.Chem., 289:6978-6990, 2014

PubMed 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.

PubMed: 24451384
DOI: 10.1074/jbc.M113.516195

Experimental method

X-RAY DIFFRACTION (1.7 Å)