User:Hollynns/Diguanylate cyclase

In enzymology, diguanylate cyclase, also known as diguanylate kinase, is an enzyme that catalyzes the chemical reaction:

2 Guanosine triphosphate ↔ 2 diphosphate + cyclic di-3',5'-guanylate

The substrates of diguanylate cyclases (DGCs) are two molecules of guanosine triphosphate (GTP) and the products are two molecules of diphosphate and one molecule of cyclic di-3’,5’-guanylate (cyclic di-GMP).

Degradation of cyclic di-GMP to guanosine monophosphate (GMP) is catalyzed by a phosphodiesterase (PDE).

Structure
DGCs are characterized by the conserved amino acid sequence motifs “GGDEF” (Gly-Gly-Asp-Glu-Phe) or “GGEEF” (Gly-Gly-Glu-Glu-Phe), which constitute the domain of the DGC active site. These domains are often found coupled to other signaling domains within multidomain proteins. Oftentimes, GGDEF domains with DGC activity and EAL domains with PDE activity are found within the same protein.

Weak sequence similarity and pronounced secondary structure similarity between GGDEF domains and the catalytic domains of adenylate cyclases (AC) have lead to the hypothesis that DGCs and ACs share a similar fold. This was verified with the resolution of the crystal structure of PleD in complex with c-di-GMP. The DCG domain closely resembles the "palm" domain of the AC catalytic core which consists of a five-stranded β-sheet surrounded by helices. Proteins with GGDEF domains often also have CheY phosphrylation receiver domains or a PAS domain (a potential oxygen sensor) [SOURCE]

Active DGC is a dimer consisting of two subunits, both with GGDEF domains [SOURCE]. The active (or catalytic) site is located at the interface between the two subunits, each binding one molecule of GTP.

As of mid 2011, 11 crystal structures of confirmed or putative DGCs have been solved, with PDB accession codes, , , , , , , , , , and.

Biological function
Diguanylate cyclase participates in the formation of the ubiquitous second messenger, cyclic-di-GMP, involved in bacterial biofilm formation and persistence. The GGDEF domain was first identified in the regulatory protein, PleD of the bacterium Caulobacter crescentus [SOURCE]. It was later noted that numerous bacterial genomes encoded multiple proteins with a GGDEF domain[SOURCE]. Pseudomonas aeruginosa PAO1 has 33 proteins with GGDEF domains, Escherichia coli K-12 has 19, and Vibrio cholerae O1 has 41. In the cell cycle of Caulobacter crescentus, DGC PleD is known to control pole morphogenesis. In Pseudomonas fluorescens DGC WspR activity is hypothesized to be partially responsible for the wrinkly spreader (WS) phenotype. In Pseudomonas aeruginosa, WspR has also been known to control autoaggregation. .

C. crescentus
During the cell cycle of "C. cresentus", proteins with GGDEF and EAL domains are separated towards the two distinct poles. At the stalked pole, the diguanylate cyclase PleD is required for the formation of the holdfast and the ejection of the flagellum.