Formation and dimerization of the phosphodiesterase active site of the Pseudomonas aeruginosa MorA, a bi-functional c-di-GMP regulator

DOI: 10.1016/j.febslet.2014.11.002
PMID: 25447517

Authors: Curtis Phippen (Centre for Biological Sciences and Institute for Life Sciences, Life Sciences Building B85, The University of Southampton) , Halina Mikolajek (Centre for Biological Sciences and Institute for Life Sciences, Life Sciences Building B85, The University of Southampton) , Henry Schlaefli (Centre for Biological Sciences and Institute for Life Sciences, Life Sciences Building B85, The University of Southampton) , Charles William Keevil (Centre for Biological Sciences and Institute for Life Sciences, Life Sciences Building B85, The University of Southampton) , Jeremy Stephen Webb (Centre for Biological Sciences and Institute for Life Sciences, Life Sciences Building B85, The University of Southampton) , Ivo Tews (Centre for Biological Sciences and Institute for Life Sciences, Life Sciences Building B85, The University of Southampton)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Febs Letters , VOL 588 (24) , PAGES 4631 - 4636

State: Published (Approved)
Published: December 2014

Abstract: Diguanylate cyclases (DGC) and phosphodiesterases (PDE), respectively synthesise and hydrolyse the secondary messenger cyclic dimeric GMP (c-di-GMP), and both activities are often found in a single protein. Intracellular c-di-GMP levels in turn regulate bacterial motility, virulence and biofilm formation. We report the first structure of a tandem DGC–PDE fragment, in which the catalytic domains are shown to be active. Two phosphodiesterase states are distinguished by active site formation. The structures, in the presence or absence of c-di-GMP, suggest that dimerisation and binding pocket formation are linked, with dimerisation being required for catalytic activity. An understanding of PDE activation is important, as biofilm dispersal via c-di-GMP hydrolysis has therapeutic effects on chronic infections.

Journal Keywords: Amino; Biocatalysis; Catalytic; Cyclic; Enzyme; Escherichia; Models; Molecular; Phosphorus-Oxygen; Protein; Quaternary; Pseudomonas aeruginosa

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Other Facilities: ESRF