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Formation and dimerization of the phosphodiesterase active site of the Pseudomonas aeruginosa MorA, a bi‐functional c‐di‐GMP regulator
Author(s) -
Phippen Curtis William,
Mikolajek Halina,
Schlaefli Henry George,
Keevil Charles William,
Webb Jeremy Stephen,
Tews Ivo
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.11.002
Subject(s) - phosphodiesterase , pseudomonas aeruginosa , biofilm , second messenger system , chemistry , active site , intracellular , motility , virulence , regulator , enzyme , hydrolase , microbiology and biotechnology , biochemistry , hydrolysis , biology , stereochemistry , bacteria , gene , genetics
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.