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

Formation and dimerization of the phosphodiesterase active site of the Pseudomonas aeruginosa MorA, a bi-functional c-di-GMP regulator
Formation and dimerization of the phosphodiesterase active site of the Pseudomonas aeruginosa MorA, a bi-functional c-di-GMP regulator
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.
MorA, diguanylate cyclases, phosphodiesterases, c-di-GMP, Biofilm dispersal
0014-5793
4631-4636
Phippen, Curtis William
ee06e5c1-815f-497f-9c67-47ead3772704
Mikolajek, Halina
c394c255-9248-4217-ace9-4a0382bfc0c5
Schlaefli, Henry George
33536fac-25b4-4569-b87f-0a0ee86b8145
Keevil, Charles William
cb7de0a7-ce33-4cfa-af52-07f99e5650eb
Webb, Jeremy Stephen
ec0a5c4e-86cc-4ae9-b390-7298f5d65f8d
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Phippen, Curtis William
ee06e5c1-815f-497f-9c67-47ead3772704
Mikolajek, Halina
c394c255-9248-4217-ace9-4a0382bfc0c5
Schlaefli, Henry George
33536fac-25b4-4569-b87f-0a0ee86b8145
Keevil, Charles William
cb7de0a7-ce33-4cfa-af52-07f99e5650eb
Webb, Jeremy Stephen
ec0a5c4e-86cc-4ae9-b390-7298f5d65f8d
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd

Phippen, Curtis William, Mikolajek, Halina, Schlaefli, Henry George, Keevil, Charles William, Webb, Jeremy Stephen and Tews, Ivo (2014) Formation and dimerization of the phosphodiesterase active site of the Pseudomonas aeruginosa MorA, a bi-functional c-di-GMP regulator. FEBS Letters, 588 (24), 4631-4636. (doi:10.1016/j.febslet.2014.11.002).

Record type: Article

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.

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FEBSLett-Tews-AcceptedManuscript.pdf - Accepted Manuscript
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More information

Accepted/In Press date: 3 November 2014
e-pub ahead of print date: 11 November 2014
Published date: 20 December 2014
Keywords: MorA, diguanylate cyclases, phosphodiesterases, c-di-GMP, Biofilm dispersal
Organisations: Molecular and Cellular

Identifiers

Local EPrints ID: 371841
URI: http://eprints.soton.ac.uk/id/eprint/371841
ISSN: 0014-5793
PURE UUID: c2714f75-07f3-47ca-9950-e6ff5f5e2ec1
ORCID for Halina Mikolajek: ORCID iD orcid.org/0000-0003-0776-9974
ORCID for Charles William Keevil: ORCID iD orcid.org/0000-0003-1917-7706
ORCID for Jeremy Stephen Webb: ORCID iD orcid.org/0000-0003-2068-8589
ORCID for Ivo Tews: ORCID iD orcid.org/0000-0002-4704-1139

Catalogue record

Date deposited: 18 Nov 2014 16:11
Last modified: 21 Nov 2021 03:03

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Contributors

Author: Curtis William Phippen
Author: Henry George Schlaefli
Author: Ivo Tews ORCID iD

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