Publication
Article Metrics
Citations
Online attention
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 DGCPDE 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