3BRE

Crystal Structure of P.aeruginosa PA3702

Summary for 3BRE

• Entry DOI: 10.2210/pdb3bre/pdb
• Descriptor: Probable two-component response regulator, MAGNESIUM ION, 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) (3 entities in total)
• Functional Keywords: protein-nucleotide complex, signaling protein
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 81236.75

Authors

De, N.,Pirruccello, M.,Krasteva, P.V.,Bae, N.,Raghavan, R.V.,Sondermann, H. (deposition date: 2007-12-21, release date: 2008-04-01, Last modification date: 2023-08-30)

Primary citation

De, N.,Pirruccello, M.,Krasteva, P.V.,Bae, N.,Raghavan, R.V.,Sondermann, H.
Phosphorylation-independent regulation of the diguanylate cyclase WspR.
Plos Biol., 6:e67-e67, 2008

PubMed Abstract: Environmental signals that trigger bacterial pathogenesis and biofilm formation are mediated by changes in the level of cyclic dimeric guanosine monophosphate (c-di-GMP), a unique eubacterial second messenger. Tight regulation of cellular c-di-GMP concentration is governed by diguanylate cyclases and phosphodiesterases, which are responsible for its production and degradation, respectively. Here, we present the crystal structure of the diguanylate cyclase WspR, a conserved GGDEF domain-containing response regulator in Gram-negative bacteria, bound to c-di-GMP at an inhibitory site. Biochemical analyses revealed that feedback regulation involves the formation of at least three distinct oligomeric states. By switching from an active to a product-inhibited dimer via a tetrameric assembly, WspR utilizes a novel mechanism for modulation of its activity through oligomerization. Moreover, our data suggest that these enzymes can be activated by phosphodiesterases. Thus, in addition to the canonical pathways via phosphorylation of the regulatory domains, both product and enzyme concentration contribute to the coordination of c-di-GMP signaling. A structural comparison reveals resemblance of the oligomeric states to assemblies of GAF domains, widely used regulatory domains in signaling molecules conserved from archaea to mammals, suggesting a similar mechanism of regulation.

PubMed: 18366254
DOI: 10.1371/journal.pbio.0060067

Experimental method

X-RAY DIFFRACTION (2.4 Å)