Information on EC 2.7.7.65 -

Information on EC 2.7.7.65 - diguanylate cyclase:

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EC NUMBER	COMMENTARY
2.7.7.65	-

RECOMMENDED NAME	GeneOntology No.
diguanylate cyclase	GO:0052621

REACTION	REACTION DIAGRAM	COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
2 GTP = 2 diphosphate + cyclic di-3',5'-guanylate		-	-	-	-
2 GTP = 2 diphosphate + cyclic di-3',5'-guanylate		-	Rhizobium leguminosarum	-	679884

REACTION TYPE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
cyclization	Rhizobium leguminosarum	-	-	679884
cyclization	Thermotoga maritima	Q9X2A8	-	701669
cyclization	Escherichia coli	-	-	701853, 702355
cyclization	Desulfotalea psychrophila	Q6ARU5	-	702469
cyclization	Anaplasma phagocytophilum	Q2GKF8	-	704312
cyclization	Pseudomonas syringae	-	-	705162
nucleotidyl group transfer	Rhizobium leguminosarum	-	-	679884
P-O bond cleavage	Rhizobium leguminosarum	-	-	679884

PATHWAY	KEGG Link	MetaCyc Link
No entries in this field

SYSTEMATIC NAME

IUBMB Comments

GTP:GTP guanylyltransferase

A GGDEF-domain-containing protein that requires Mg2+ or Mn2+ for activity. The enzyme can be activated by BeF3, a phosphoryl mimic, which results in dimerization [3]. Dimerization is required but is not sufficient for diguanylate-cyclase activity [3]. Cyclic di-3',5'-guanylate is an intracellular signalling molecule that controls motility and adhesion in bacterial cells. It was first identified as having a positive allosteric effect on EC 2.4.1.12, cellulose synthase (UDP-forming) [1].

SYNONYMS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
AdrA	Escherichia coli	-	-	701853
ALL2874	Anabaena sp.	-	encoded by gene all2874	692878
BifA	Pseudomonas aeruginosa	-	-	680510
DGC	Gluconacetobacter xylinus	-	-	680432
DGC	Thermotoga maritima	Q9X2A8	-	701669
DGC	Escherichia coli	-	-	701853, 702355
Dgc1	Gluconacetobacter xylinus	-	-	679884
diguanylate cyclase	Caulobacter vibrioides	Q9A5I5	-	680826, 682885
diguanylate cyclase	Anabaena sp.	-	-	692878
diguanylate cyclase	Pseudomonas syringae	-	-	694796, 705162
diguanylate cyclase	Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida	-	-	694796
diguanylate cyclase	Thermotoga maritima	Q9X2A8	-	701669
diguanylate cyclase	Escherichia coli	-	-	701853, 702355
diguanylate cyclase	Desulfotalea psychrophila	Q6ARU5	-	702469
diguanylate cyclase	Anaplasma phagocytophilum	Q2GKF8	-	704312
direct oxygen sensing cyclase	Escherichia coli	P0AA89	-	702355
DosC	Escherichia coli	P0AA89	-	702355
EcDosC	Escherichia coli	P0AA89	-	702355
HemDGC	Desulfotalea psychrophila	Q6ARU5	-	702469
heme-containing diguanylate cyclase	Desulfotalea psychrophila	Q6ARU5	-	702469
MifA	Aliivibrio fischeri	-	-	680474
MifB	Aliivibrio fischeri	-	-	680474
PA4367	Pseudomonas aeruginosa	-	-	680510
PleD	Caulobacter vibrioides	-	-	680007, 680826
PleD	Caulobacter vibrioides	-	response regulator with diguanylate cyclase (GGDEF) domain, Rec domain (D1) and Rec-like adaptor domain (D2)	682885
PleD	Anaplasma phagocytophilum	Q2GKF8	-	704312
Rrp1	Borrelia burgdorferi	-	-	680449
tDGC	Thermotoga maritima	Q9X2A8	-	701669
thermophilic diguanylate cyclase domain protein	Thermotoga maritima	Q9X2A8	-	701669
WspR	Pseudomonas aeruginosa	-	locus tag PA3702	694796
WspR	Pseudomonas fluorescens	-	locus tag Pfl__1058	694796
WspR	Pseudomonas putida	-	locus tag PP__1494	694796
WspR	Pseudomonas syringae	-	locus tag PSPTO__1499	694796
WspR	Pseudomonas syringae	-	-	705162
YddV	Escherichia coli	-	-	680795
YhcK	Escherichia coli	-	-	679884

CAS REGISTRY NUMBER	COMMENTARY
146316-82-7	-

ORGANISM	COMMENTARY	LITERATURE	SEQUENCE CODE	SEQUENCE DB	SOURCE
Aliivibrio fischeri	-	680474	-	-
Anabaena sp.	strain PCC 7120	692878	-	-
Anaplasma phagocytophilum	-	704312	Q2GKF8	UniProt
Borrelia burgdorferi	-	680449	-	-
Caulobacter vibrioides	-	680007	-	-
Caulobacter vibrioides	-	680703	Q9A3B9	Swissprot
Caulobacter vibrioides	-	680826, 682885	Q9A5I5	UniProt
Caulobacter vibrioides	isoform PleD	680826, 682502, 682885	-	-
Desulfotalea psychrophila	-	702469	Q6ARU5	UniProt
Escherichia coli	-	679884, 680795, 701853	-	-
Escherichia coli	-	702355	P0AA89	UniProt
Gluconacetobacter xylinus	-	679884, 682337, 682338	-	-
Gluconacetobacter xylinus	isoforms Cdg1, Cdg2, Cdg3. Cdg1 contributes 80% of cellular enzymic activites, Cdg2 and Cdg3 contribute 15 and 5%, resp.	680432	-	-
Pseudomonas aeruginosa	PAO1	694796	-	-
Pseudomonas aeruginosa	strain PA14, gene PA4367 encodes a protein with an EAL domain associated with cyclic di-3�,5�-guanylate phosphodiesterase activity, and a DDGEF domain associated with cyclic di-3�,5�-guanylate cyclase activity	680510	-	-
Pseudomonas fluorescens	PfO-1	694796	-	-
Pseudomonas putida	KT2440	694796	-	-
Pseudomonas syringae	-	705162	-	-
Pseudomonas syringae	DC3000	694796	-	-
Rhizobium leguminosarum	-	679884	-	-
Rhodobacter sphaeroides	strain RSP3513	680449	-	-
Rhodobacter sphaeroides RSP3513	strain RSP3513	680449	-	-
Thermotoga maritima	-	701669	Q9X2A8	UniProt
Xanthomonas axonopodis	-	681997	-	-

GENERAL INFORMATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
physiological function	Escherichia coli	-	in Gram-negative bacteria production of of cyclic di-3',5'-guanylate, c-di-GMP, is the main trigger for production of extracellular polysaccharides and for biofilm formation	701853

SUBSTRATE	PRODUCT	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY/ Substrate	LITERATURE/ Substrate	COMMENTARY/ Product	LITERATURE/ Product	Reversibility r=reversible ir=irreversible ?=not specified
GTP	cyclic di-3',5'-guanylate + diphosphate		Aliivibrio fischeri	-	-	680474	-	-	?
GTP	cyclic di-3',5'-guanylate + diphosphate		Escherichia coli	-	-	679884	-	-	?
GTP	cyclic di-3',5'-guanylate + diphosphate		Rhodobacter sphaeroides	-	-	680449	-	-	?
GTP	cyclic di-3',5'-guanylate + diphosphate		Gluconacetobacter xylinus	-	-	679884	-	-	?
GTP	cyclic di-3',5'-guanylate + diphosphate		Caulobacter vibrioides	-	-	680007, 680826	-	-	?
GTP	cyclic di-3',5'-guanylate + diphosphate		Caulobacter vibrioides	Q9A5I5	-	680826	-	-	?
GTP	cyclic di-3',5'-guanylate + diphosphate		Rhizobium leguminosarum	-	-	679884	-	-	?
GTP	cyclic di-3',5'-guanylate + diphosphate		Borrelia burgdorferi	-	-	680449	-	-	?
GTP	cyclic di-3',5'-guanylate + diphosphate		Caulobacter vibrioides	Q9A3B9	-	680703	-	-	?
GTP	cyclic di-3',5'-guanylate + diphosphate		Caulobacter vibrioides	-	diguanylate cyclase activity constitutes the signaling output of the PleD response regulator	680007	-	-	?
GTP	diphosphate + cyclic di-3',5'-guanylate		Escherichia coli	-	-	701853	-	-	?
GTP	diphosphate + cyclic di-3',5'-guanylate		Pseudomonas syringae	-	-	705162	-	-	?
GTP	diphosphate + cyclic di-3',5'-guanylate		Thermotoga maritima	Q9X2A8	-	701669	-	-	?
GTP	diphosphate + cyclic di-3',5'-guanylate		Escherichia coli	P0AA89	-	702355	-	-	?
GTP	diphosphate + cyclic di-3',5'-guanylate		Desulfotalea psychrophila	Q6ARU5	-	702469	-	-	?
GTP	diphosphate + cyclic di-3',5'-guanylate		Anaplasma phagocytophilum	Q2GKF8	-	704312	-	-	?
GTP + GTP	cyclic di-3',5'-guanylate + diphosphate + diphosphate		Caulobacter vibrioides	-	-	682885	analyses by pyrophosphatase-coupled spectrophotometric assay	-	?
GTP + GTP	cyclic di-3',5'-guanylate + diphosphate + diphosphate		Pseudomonas aeruginosa	-	2 mM Mg2+	694796	analysis by coupled spectrophotometric assay measuring diphosphate synthesis or by reverse-phase HPLC	-	?
GTP + GTP	cyclic di-3',5'-guanylate + diphosphate + diphosphate		Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae	-	2 mM Mg2+, 25�C	694796	analysis by coupled spectrophotometric assay measuring diphosphate synthesis or by reverse-phase HPLC	-	?
GTP + GTP	cyclic di-3',5'-guanylate + diphosphate + diphosphate		Anabaena sp.	-	pH 8, 60 min, 25�C, 10 mM MgCl2	692878	reaction stop by 0.083 mM EDTA	-	?
GTP + GTP	cyclic-di-3',5'-GMP + diphosphate + diphosphate		Caulobacter vibrioides	Q9A5I5	pH 7.8	680826	reaction stop with 25 mM EDTA, pH 6, KD (cyclic-di-3�,5�-GMP): 0.3 microM or 0.4 microM (in presence of activator BeF3)	-	?
additional information	?	-	Escherichia coli	-	cyclic guanylate cyclase YvvD and Dos, a heme based oxygen sensor with cyclic diguanylate phosphodiesterase activity may be part of a fine-tuning mechanism for regulating the intracellular levels of cyclic diguanylate	680795	-	-	-
additional information	?	-	Aliivibrio fischeri	-	MifA and MifB proteins act posttranscriptionally on flagellation	680474	-	-	-
additional information	?	-	Rhodobacter sphaeroides	-	no substrate: ATP, ADP, AMP, GDP, GMP,CTP, TTP, c-di-GMP, cAMP, and cGMP	680449	-	-	-
additional information	?	-	Pseudomonas aeruginosa	-	purified enzyme shows phosphodiesterase activity, but no diguanylate cyclase activity	680510	-	-	-
additional information	?	-	Caulobacter vibrioides	-	mode of GTPalphaS/Mg2+-binding suggests two-metal catalytic mechanism analogous to adenylate cyclases, on-rates constants of substrate and product range between 100/sec and 300/sec	682885	-	-	-
additional information	?	-	Pseudomonas aeruginosa	-	pppGpG co-purified with reaction products, possible intermediate of diguanylate cyclisation	694796	-	-	-

NATURAL SUBSTRATES	NATURAL PRODUCTS	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY SUBSTRATE	LITERATURE (Substrate)	COMMENTARY PRODUCT	LITERATURE (Product)
GTP	cyclic di-3',5'-guanylate + diphosphate		Caulobacter vibrioides	-	diguanylate cyclase activity constitutes the signaling output of the PleD response regulator	680007	-	-
GTP	diphosphate + cyclic di-3',5'-guanylate		Escherichia coli	-	-	701853	-	-
GTP	diphosphate + cyclic di-3',5'-guanylate		Pseudomonas syringae	-	-	705162	-	-
GTP	diphosphate + cyclic di-3',5'-guanylate		Thermotoga maritima	Q9X2A8	-	701669	-	-
GTP	diphosphate + cyclic di-3',5'-guanylate		Escherichia coli	P0AA89	-	702355	-	-
GTP	diphosphate + cyclic di-3',5'-guanylate		Desulfotalea psychrophila	Q6ARU5	-	702469	-	-
GTP	diphosphate + cyclic di-3',5'-guanylate		Anaplasma phagocytophilum	Q2GKF8	-	704312	-	-
additional information	?	-	Escherichia coli	-	cyclic guanylate cyclase YvvD and Dos, a heme based oxygen sensor with cyclic diguanylate phosphodiesterase activity may be part of a fine-tuning mechanism for regulating the intracellular levels of cyclic diguanylate	680795	-	-
additional information	?	-	Aliivibrio fischeri	-	MifA and MifB proteins act posttranscriptionally on flagellation	680474	-	-

COFACTOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
heme	Escherichia coli	P0AA89	-	702355	2D-image
heme	Desulfotalea psychrophila	Q6ARU5	-	702469	2D-image

METALS and IONS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
Mg2+	Caulobacter vibrioides	-	; or Mn2+, strictly required, with Mn2+ resulting in slightly higher activity than Mg2+	680826
Mg2+	Caulobacter vibrioides	-	enhances dimerisation	682885
Mg2+	Thermotoga maritima	Q9X2A8	-	701669
Mn2+	Caulobacter vibrioides	-	or Mg2+, strictly required, with Mn2+ resulting in slightly higher activity than Mg2+; slightly higher activation than Mg2+	680826
Mn2+	Caulobacter vibrioides	-	enhances dimerisation more than Mg2+	682885

INHIBITORS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
3-O-alpha-L-rhamnopyranosyl-(1-2)-beta-D-galactopyranosyl-(1-2)-beta-D-glucuronopyranosyl soyasapogenol B 22-O-alpha-D-glucopyranoside	Gluconacetobacter xylinus	-	-	682337	2D-image
3-O-alpha-L-rhamnopyranosyl-(1-2)-beta-D-galactopyranosyl-(1-2)-beta-D-glucuronopyranosyl soyasapogenol B 22-O-alpha-D-glucopyranoside	Gluconacetobacter xylinus	-	noncompetitive, inhibition is decreased by 50% in presence of 0.02 mM cyclic diguanylate, no inhibition in presence of detergents. Inhibitor affects binding of cyclic diguanylate to enzyme. In situ, inhibitor affects bacterial cellulose synthesis and enzyme activity	682338	2D-image
cyclic 3',5'-diguanylate	Caulobacter vibrioides	-	product inhibition is due to domain immobilization and sets an upper limit for the concentration of this second messenger in the cell	682502	2D-image
cyclic di-3',5'-guanlylate	Caulobacter vibrioides	-	strong product inhibition	680007	2D-image
cyclic di-3',5'-guanylate	Pseudomonas syringae	-	product inhibition	705162	2D-image
cyclic diguanylate	Caulobacter vibrioides	-	noncompetitive, product inhibition	682885	2D-image
cyclic-di-3',5'-GMP	Caulobacter vibrioides	-	allosteric feedback, product inhibition, independent of activation status, binding induces change in conformation and protein-solvent interactions	680826	2D-image
D-glucuronopyranosyl soyasapogenol B 22-O-alpha-D-glucopyranoside	Gluconacetobacter xylinus	-	isolated from Pisum sativum, specific and highly potent inhibition of enzyme	682337	2D-image
GTP	Caulobacter vibrioides	-	-	682885	2D-image
KCl	Caulobacter vibrioides	-	25 mM, slight decrease in activity	680826	2D-image
NaCl	Caulobacter vibrioides	-	activity decreases with increasing concentrations of NaCl	680826	2D-image
papulacandin B	Gluconacetobacter xylinus	-	-	682338	2D-image
sulfathiazole	Escherichia coli	-	-	701853	2D-image

ACTIVATING COMPOUND	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
BeF3-	Pseudomonas syringae	-	-	705162	2D-image
beryllium fluoride	Caulobacter vibrioides	-	BeF3, phosphoryl mimic, optimum concentration: 1 mM BeCl2/10 mM NaF (nonspecifcally inhibitory at higher concentrations), causes dimerisation and cyclic di-3�,5�-guanylate synthesis, no influence on cyclic-di-GMP binding affinity and thus allosteric regulation	680826	2D-image
beryllium fluoride	Caulobacter vibrioides	-	BeF3-, pseudo-phosphorylation, enhances dimerisation by lowering KD to less than 10 microM, tightens dimer interface between two D1/D2 domains, modification activates enzyme	682885	2D-image
O2	Escherichia coli	P0AA89	-	702355	2D-image
O2	Desulfotalea psychrophila	Q6ARU5	-	702469	2D-image
beryllium trifluoride	Caulobacter vibrioides	-	activation by beryllium trifluoride may substitute for activation by phosphorylation	680826	-
additional information	Pseudomonas syringae	-	oligomerization-dependent activation of WspR, the stalks are key regulatory elements for the oligomerization, activation, and autoinhibition of WspR	705162	-

KM VALUE [mM]	KM VALUE [mM] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.00597	-	GTP	Pseudomonas syringae	-	WspR full-length, cyclic di-3',5'-guanylate-free	705162	2D-image
0.01296	-	GTP	Pseudomonas syringae	-	WspGCN4-RGGDEF, cyclic di-3',5'-guanylate-free	705162	2D-image
0.01307	-	GTP	Pseudomonas syringae	-	WspGCN4-RGGDEF, cyclic di-3',5'-guanylate-bound	705162	2D-image

TURNOVER NUMBER [1/s]	TURNOVER NUMBER MAXIMUM[1/s]	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
4.5	-	GTP	Pseudomonas syringae	-	WspR full-length, cyclic di-3',5'-guanylate-free	705162	2D-image
40.56	-	GTP	Pseudomonas syringae	-	WspGCN4-RGGDEF, cyclic di-3',5'-guanylate-bound	705162	2D-image
59.05	-	GTP	Pseudomonas syringae	-	WspGCN4-RGGDEF, cyclic di-3',5'-guanylate-free	705162	2D-image
0.0433	-	additional information	Thermotoga maritima	Q9X2A8	R158A mutant	701669	-

kcat/KM VALUE [1/mMs^-1]	kcat/KM VALUE [1/mMs^-1] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

Ki VALUE [mM]	Ki VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.005	-	3-O-alpha-L-rhamnopyranosyl-(1-2)-beta-D-galactopyranosyl-(1-2)-beta-D-glucuronopyranosyl soyasapogenol B 22-O-alpha-D-glucopyranoside	Gluconacetobacter xylinus	-	pH 7.5, 30�C	682338	2D-image
0.07	-	papulacandin B	Gluconacetobacter xylinus	-	pH 7.5, 30�C	682338	2D-image

IC50 VALUE [mM]	IC50 VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.007	-	GTP	Caulobacter vibrioides	-	wild-type	682885	2D-image
0.009	-	GTP	Caulobacter vibrioides	-	mutant R313A	682885	2D-image
0.017	-	GTP	Caulobacter vibrioides	-	double mutant R148A/R178A	682885	2D-image
0.03	-	GTP	Caulobacter vibrioides	-	triple mutant R148A/R178A/R313A	682885	2D-image

SPECIFIC ACTIVITY [µmol/min/mg]	SPECIFIC ACTIVITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
3.6e-05	-	Caulobacter vibrioides	-	mutant Y26A, in presence of BeF3 (1 mM BeCl2, 10 mM NaF)	680826
4e-05	-	Caulobacter vibrioides	-	mutant Y26A in presence of beryllium trifluoride, pH 7.8	680826
0.0011	-	Caulobacter vibrioides	-	mutant D53N, in presence of BeF3 (1 mM BeCl2, 10 mM NaF); mutant D53N in presence of beryllium trifluoride, pH 7.8	680826
0.00238	-	Caulobacter vibrioides	-	mutant D53N	680826
0.0024	-	Caulobacter vibrioides	-	mutant D53N in absence of beryllium trifluoride, pH 7.8	680826
0.0033	-	Caulobacter vibrioides	-	wild-type in absence of beryllium trifluoride, pH 7.8	680826
0.00332	-	Caulobacter vibrioides	-	wild-type	680826
0.16	-	Caulobacter vibrioides	-	wild-type, in presence of BeF3 (1 mM BeCl2, 10 mM NaF); wild-type in presence of beryllium trifluoride, pH 7.8	680826
additional information	-	Caulobacter vibrioides	-	no detectable activity for mutant Y26A	680826
additional information	-	Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae	-	increased activity in presence of phosphodiesterases through hydrolysis of cyclic di-3�,5�-guanylate thus reduction of product inhibition	694796

pH OPTIMUM	pH MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
7.5	-	Thermotoga maritima	Q9X2A8	R158A mutant	701669
7.5	-	Escherichia coli	P0AA89	activity assay	702355
8	-	Caulobacter vibrioides	-	maximum activity between pH 7.5 and 8.5	680826
8	-	Desulfotalea psychrophila	Q6ARU5	activity assay	702469

pH RANGE	pH RANGE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
6.5	10	Caulobacter vibrioides	-	enzymatically active	680826

TEMPERATURE OPTIMUM	TEMPERATURE OPTIMUM MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
30	-	Escherichia coli	P0AA89	activity assay	702355
30	-	Desulfotalea psychrophila	Q6ARU5	activity assay	702469
55	-	Thermotoga maritima	Q9X2A8	R158A mutant	701669

TEMPERATURE RANGE	TEMPERATURE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

pI VALUE	pI VALUE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

SOURCE TISSUE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	SOURCE
heterocyst	Anabaena sp.	-	heterocyst differentiation pathway (upstream of HetR), decreased heterocyst frequency and block of heterocyst differentiation within 4 days in mutant strain depleted for all2874 gene and grown in absence of source of combined nitrogen	692878
vegetative cell	Anabaena sp.	-	-	692878

LOCALIZATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	GeneOntology No.	LITERATURE	SOURCE
cell pole	Caulobacter vibrioides	-	response regulator PleD-GFP protein specifically localizes to the stalked pole and is absent from the flagellated swarmer pole. Targeting of PleD to the cell pole is coupled to the activation of its C-terminal di-guanylate cyclase domain	60187	680007
cell pole	Caulobacter vibrioides	-	recruitment to predivisional pole during cell cycle of differentiating cells dependends on dimerisation	60187	680826
membrane	Gluconacetobacter xylinus	-	isoform Dgc1 has two possible transmembrane helices and Dgc2 has one	16020	680432
membrane	Aliivibrio fischeri	-	both MifA and MifB are membrane-associated	16020	680474
membrane	Pseudomonas aeruginosa	-	inner membrane	16020	680510

PDB	SCOP	CATH	ORGANISM
2wb4, download	SCOP (2wb4)	CATH (2wb4)	Caulobacter crescentus (strain ATCC 19089 / CB15)
3t9o, download	SCOP (3t9o)	CATH (3t9o)	Escherichia coli (strain K12)
3tvk, download	SCOP (3tvk)	CATH (3tvk)	Escherichia coli (strain K12)
3ign, download	SCOP (3ign)	CATH (3ign)	Marinobacter aquaeolei (strain ATCC 700491 / DSM 11845 / VT8)
3hva, download	SCOP (3hva)	CATH (3hva)	Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)

MOLECULAR WEIGHT	MOLECULAR WEIGHT MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
18000	-	Escherichia coli	P0AA89	DosCH fragment, codon 2-160, determined by SDS-PAGE	702355
21000	-	Thermotoga maritima	Q9X2A8	determined by SDS-PAGE	701669
39170	-	Pseudomonas aeruginosa	-	theoretical, hexa-His-tagged wild-type; wild-type, LC-ESI-MS	694796
42000	-	Desulfotalea psychrophila	Q6ARU5	monomer	702469
50000	-	Escherichia coli	P0AA89	DosC purified from Escherichia coli moderately overexpressing the wild-type dosCP operon, determined by SDS-PAGE	702355
52000	-	Anaplasma phagocytophilum	Q2GKF8	native Anaplasma phagocytophilum PleD, determined by SDS-PAGE and Western Blot analysis; theoretical	704312
55000	-	Pseudomonas aeruginosa	-	mutant L167D, gel-filtration, monomer or weakly associated dimer	694796
56000	-	Anaplasma phagocytophilum	Q2GKF8	recombinant PleD, determined by SDS-PAGE and Western Blot analysis	704312
73300	-	Pseudomonas aeruginosa	-	mutant L170D, coupled gel-filtration/multiangle light scattering, tetramer	694796
78600	-	Pseudomonas aeruginosa	-	mutant R242A, coupled gel-filtration/multiangle light scattering, dimer	694796
80100	-	Pseudomonas aeruginosa	-	mutant R198/242A, coupled gel-filtration/multiangle light scattering, dimer	694796
81300	-	Pseudomonas aeruginosa	-	mutant R198A, coupled gel-filtration/multiangle light scattering, dimer; wild-type (phosphodiesterase-treated) and GGAAF mutant, coupled gel-filtration/multiangle light scattering, dimer	694796
85900	-	Pseudomonas aeruginosa	-	wild-type, coupled gel-filtration/multiangle light scattering, dimer	694796
95000	-	Escherichia coli	P0AA89	MBP-DosC, determined by SDS-PAGE	702355
161200	-	Pseudomonas aeruginosa	-	mutant R198/242A, coupled gel-filtration/multiangle light scattering, tetramer	694796
161300	-	Pseudomonas aeruginosa	-	mutant L170D, coupled gel-filtration/multiangle light scattering, tetramer	694796
161600	-	Pseudomonas aeruginosa	-	mutant R198A, coupled gel-filtration/multiangle light scattering, tetramer	694796
162100	-	Pseudomonas aeruginosa	-	mutant R242A, coupled gel-filtration/multiangle light scattering, tetramer	694796
162700	-	Pseudomonas aeruginosa	-	GGAAF mutant, coupled gel-filtration/multiangle light scattering, tetramer	694796
170000	-	Desulfotalea psychrophila	Q6ARU5	determined by Blue-Native PAGE, homotetramer	702469

SUBUNITS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
?	Pseudomonas aeruginosa	-	x * 78000, calculated	680510
dimer	Caulobacter vibrioides	-	enzymatically active state, concentration dependent, crosslinking (using disuccinimidyl suberate, DSS)	680826
dimer	Caulobacter vibrioides	-	at high protein concentrations and/or presence of divalent metal ions (Mg2+, Mn2+), tightened upon BeF3-modification, exothermic dimerisation, KD: 100 microM, gel filtration chromatography and crystallography	682885
dimer	Pseudomonas aeruginosa	-	compact structure, globular shape, active state, phosphodiesterase-treated (hydrolysis of bound cyclic di-3�,5�-guanylate) and nucleotide-free wild-type, nucleotide-free mutants GGAAF, R242A and R198A and cyclic di-3�,5�-guanylate-bound mutant L170D, coupled gel-filtration/multiangle light scattering; elongated shape, product-inhibited state, purified wild-type (cyclic di-3�,5�-guanylate-bound), coupled gel-filtration/multiangle light scattering	694796
dimer	Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae	-	compact structure, globular shape, active state, phosphodiesterase-treated (hydrolysis of bound cyclic di-3�,5�-guanylate) and nucleotide-free wild-type, coupled gel-filtration/multiangle light scattering; elongated shape, product-inhibited state, purified wild-type (cyclic di-3�,5�-guanylate-bound), coupled gel-filtration/multiangle light scattering	694796
dimer	Thermotoga maritima	Q9X2A8	wild-type	701669
homodimer	Escherichia coli	P0AA89	DosCH fragment	702355
homotetramer	Desulfotalea psychrophila	Q6ARU5	4 * 42000	702469
homotetramer	Pseudomonas syringae	-	-	705162
tetramer	Pseudomonas aeruginosa	-	transient intermediate state between active, compact dimer and product-inhibited, elongated dimer, induced by high enzyme concentration, nucleotide-depleted wild-type sample, nucleotide-free mutants GGAAF, R242A and R198A and cyclic di-3�,5�-guanylate-bound mutant L170D, crystallography, coupled gel-filtration/multiangle light scattering	694796
tetramer	Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae	-	transient intermediate state between active, compact dimer and product-inhibited, elongated dimer, induced by high enzyme concentration, nucleotide-depleted wild-type, coupled gel-filtration/multiangle light scattering	694796
monomer	Thermotoga maritima	Q9X2A8	R158A mutant	701669
additional information	Escherichia coli, Gluconacetobacter xylinus, Rhizobium leguminosarum	-	the GGDEF domain is responsible for the diguanylate cyclase activity	679884
additional information	Borrelia burgdorferi, Rhodobacter sphaeroides	-	the GGDEF domain is sufficient to encode catalytic activity, which is highly regulated by the adjacent sensory protein domain	680449
additional information	Caulobacter vibrioides	-	dimer is the catalytically active state of enzyme	680826
additional information	Xanthomonas axonopodis	-	the HD-GYP phosphodiesterase domain of RpfG, which is part of a system necessary for the diffusible signalling factor dependent production of extracellular pathogenicity, interacts directly with diguanylate cyclase GGDEF domain-containing proteins. Physical linkage between quorum-sensing and cyclic diguanylate signalling pathways	681997
additional information	Pseudomonas aeruginosa	-	compact and elongated dimeric conformation correspond to catalytically active and inactive state, respectively; higher-order oligomerisation depends on interactions of stalk motifs	694796
additional information	Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae	-	compact and elongated dimeric conformation correspond to catalytically active and inactive state, respectively	694796

POSTTRANSLATIONAL MODIFICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
phosphoprotein	Caulobacter vibrioides	-	localization of response regulator PleD to the stalked pole requires its activation by phosphorylation and is dependent on the polar kinases DivJ and PleC	680007
phosphoprotein	Caulobacter vibrioides	-	enzyme is activated by phosphorylation of residue D53. In vitro, enzyme PleD can be activated by beryllium fluoride, resulting in dimerization and synthesis of cyclic diguanylate	680826
phosphoprotein	Pseudomonas syringae	-	-	705162
phosphoprotein	Borrelia burgdorferi	-	phosphorylation is required for catalytic activity	680449
additional information	Caulobacter vibrioides	-	pseudo-phosphorylation by beryllium fluoride (BeF3-) modification at residue Asp53 in Rec-domain (D1), tightens dimer	682885

Crystallization/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
after activation by berillium trifluoride. Activation causes rearrangement of an adaptor domain which in turn promotes dimer formation. The substrate analogue GTPgammaS and two putative cations are bound to the active sites. Identification of a second cyclic diguanylate binding mode that crosslinks the diguanylate cyclase domains within a protein dimer and results in noncompetitive product inhibition; BeF3-/Mg2+-modified PleD (100 microM) in presence of cyclic di-3�,5�-guanylate (0.2 mM) and substrate-analog GTPalphaS (1 mM), hanging-drop vapour-diffusion: equal volumes protein solution (10 mg/ml) and precipitant solution (0.1M HEPES pH 8, 0.73 M Na2SO4), crystals: needle shape, space group: P2(1)2(1)2(1), unit cell parameters: a: 128.9, b: 132.6, c: 88.4, resolved by molecular replacement using PDB: 1W25 as model, tightened dimer interface at the dyad symmetric stem between D1/D2 domains of the two monomers upon rotation of D2 relative to D1, restructured beta4alpha4 loop compared to nonactivated state, GTPalphaS bound to both diguanylate cyclase (GGDEF) domain active sites, 2fold symmetric crosslinking of GGDEF domains of the structural dimer in presence of cyclic di-3�,5�-guanylate, cyclic di-3�,5�-guanylate bound to allosteric (inhibitory) site similarly to nonactivated state	Caulobacter vibrioides	-	682885
in complex with product cyclic diguanylate. The guanine base is H-bonded to N335 and D344, whereas the ribosyl and alpha-phosphate moieties extend over the beta2-beta3-hairpin that carries the GGEEF signature motif. In the crystal, cyclic diguanylate molecules are crosslinking active sites of adjacent dimers. In solution, two diguanylate cyclase doamins of a dimer may align in a twofold symmetric way to catalyze synthesis of cyclic diguanylate	Caulobacter vibrioides	-	682502
in complex with cyclic di-3�,5�-guanylate (PDB: 3BRE), solved by molecular replacement using PDB: 1W25 as model, tetramer of two anti-parallel dimers with physically blocked active site, hanging-drop vapour-diffusion: equal volumes protein solution (5-30 mg/ml) and reservoir solution (0.1 M Tris-HCl pH 8, 2.9 M NaCl, 15% xylitol), crystal: space group: C2, unit cell parameter: a: 144.5, b: 72.8, c: 106.1, beta: 110.8, asymmetric unit: two molecules with active site facing each other and four molecules cyclic di-3�,5�-guanylate bound to residues Arg242 and Arg198 and two Mg2+ ions, resemblance of GAF domain assembly	Pseudomonas aeruginosa	-	694796
the crystal structure of full-length WspR is determined at 2.8 A resolution, of WspGCN4-RGGDEF at 1.94 A resolution	Pseudomonas syringae	-	705162

pH STABILITY	pH STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

TEMPERATURE STABILITY	TEMPERATURE STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

GENERAL STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
activity decreases with increasing NaCl concentration and in presence of KCl (25 mM)	Caulobacter vibrioides	-	680826

ORGANIC SOLVENT	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

OXIDATION STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

STORAGE STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
-80�C, 25 mM Tris-HCl pH 7.5 including 100 mM NaCl and 1 mM dithiothreitol	Pseudomonas aeruginosa	-	694796

Purification/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
from bacterial lysate by metal affinity chromatography using HisTrap HP column and FPLC (elution: linear imidazole gradient) and dialysis	Anabaena sp.	-	692878
using a His-Select cartridge	Anaplasma phagocytophilum	Q2GKF8	704312
recombinant protein	Borrelia burgdorferi	-	680449
immobilized metal affinity chromatography followed by dialysis and analytical or preparative size exclusion chromatography on Superdex 200 column	Caulobacter vibrioides	-	680826
metal affinity chromatography (elution with 200 mM imidazole) followed by size-exclusion chromatography on Superdex 200 HR 26/60 column and analytical size-exclusion chromatography on Superdex 200 HR 10/30 column	Caulobacter vibrioides	-	682885
recombinant protein	Caulobacter vibrioides	-	680007
using a TALON metal affinity resin and a Superdex 200 column	Desulfotalea psychrophila	Q6ARU5	702469
on a Sephadex G25 and a DEAE-Sepharose column, furthermore an amylose-resin matrix is used	Escherichia coli	P0AA89	702355
application of membrane-free extract on GTP-agarose column	Gluconacetobacter xylinus	-	680432
from bacterial lysate by metal affinity chromatography and gel-filtration (size-exclusion chromatography), product cyclic di-3�,5�-guanylate co-purified with wild-type and mutants L170D and L167D from bacterial extracts despite dialysis, nucleotide-free wild-type generated by treatment with phosphodiesterase and subsequent metal affinity chromatography and gel-filtration	Pseudomonas aeruginosa	-	694796
from bacterial lysate by metal affinity chromatography and gel-filtration, product cyclic di-3�,5�-guanylate co-purified with wild-type from bacterial extracts despite dialysis, nucleotide-free wild-type generated by treatment with phosphodiesterase and subsequent metal affinity chromatography and gel-filtration	Pseudomonas fluorescens, Pseudomonas putida	-	694796
by Ni-NTA affinity chromatography, furthermore a Superdex 200 and a gel filtration column are used	Pseudomonas syringae	-	705162
from bacterial lysate by metal affinity chromatography and gel-filtration, product cyclic di-3�,5�-guanylate co-purified with wild-type from bacterial extracts despite dialysis, nucleotide-free wild-type generated by treatment with phosphodiesterase and subsequent metal affinity chromatography and gel-filtration	Pseudomonas syringae	-	694796
recombinant protein	Rhodobacter sphaeroides	-	680449
using Ni2+-nitrilotriacetic acid resin and a gel filtration coumn	Thermotoga maritima	Q9X2A8	701669

Cloned/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
expression of MifA or MifB by medium-copy plasmids inhibits motility of Vibrio fischeri. Expression by multicopy plasmids induces further phenotypes correlated with diguanylate cyclase activity such as cellulose biosynthesis and biofilm formation. High-copy expression in Escherichia coli	Aliivibrio fischeri	-	680474
630-bp internal fragment from bacterial DNA in suicide plasmid pRL277 for construction of suicide plasmid pAM4108 and generation of mutant strains by homologous recombination, complete ORF in pAM2770 for generation of pAM4114 for complementation studies, complete ORF in pEZ-30b(+) (pAM4097) for expression with C-terminal hexa-His-tag in Escherichia coli BL21(DE3)	Anabaena sp.	-	692878
into the vector pET-33b+ for expression in Escherichia coli BL21DE3 cells	Anaplasma phagocytophilum	Q2GKF8	704312
overexpressed as an amino-terminal MBP fusion in Escherichia coli	Borrelia burgdorferi	-	680449
expression as GFP fusion protein for subcellular targeting, expression with His-tag in Escherichia coli	Caulobacter vibrioides	-	680007
for expression with His-tag or as GFP-fusion protein	Caulobacter vibrioides	-	680826
in pBR322 for inducible expression with C-terminal hexa-His-tag in Escherichia coli BL21(DE3)pLysS	Caulobacter vibrioides	-	682885
into the vector pET3a for expression in Escherichia coli BL21DE3 cells	Desulfotalea psychrophila	Q6ARU5	702469
into an Escherichia coli pUC19-based expression vector and into the vector pMAL-c2e	Escherichia coli	P0AA89	702355
into the pTOPO vector	Escherichia coli	-	701853
overexpression activates cellulose synthesis in Rhizobium leguminosum and in Agrobacterium tumefaciens	Escherichia coli, Gluconacetobacter xylinus	-	679884
expression in Escherichia coli with His-tag	Pseudomonas aeruginosa	-	680510
from genomic DNA in pET21 for inducible expression with C-terminal hexa-His-tag in Escherichia coli BL21(DE3)	Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae	-	694796
the vectors pET21 and pProExHT are used	Pseudomonas syringae	-	705162
overexpression activates cellulose synthesis in Rhizobium leguminosum and in Agrobacterium tumefaciens	Rhizobium leguminosarum	-	679884
overexpressed as an amino-terminal MBP fusion in Escherichia coli	Rhodobacter sphaeroides	-	680449
a DNA construct encoding the C-terminus of the TM1788 gene is cloned into the vector pET28b+ for expression in Escherichia col BL21DE3 cells	Thermotoga maritima	Q9X2A8	701669

EXPRESSION	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

ENGINEERING	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
D327A	Caulobacter vibrioides	-	inactive due to loss of coordination of Mg2+	682885
D53N	Caulobacter vibrioides	-	less than 1% of wild-type activity; no activation by BeF3, lack of phosphoryl acceptor site	680826
DELTAR359/DELTAD362	Caulobacter vibrioides	Q9A3B9	mutations in allosteric binding site of cyclic diguanylate, abolish cyclic diguanylate binding, strong decrease in catalytic activity	680703
E370Q	Caulobacter vibrioides	Q9A3B9	mutation in active site, complete loss of catalytic activity without effect on allosteric binding of cyclic diguanylate	680703
E370Q	Caulobacter vibrioides	-	mainly dimeric, inactive mutant of the guanylate cyclase domain GG(D/E)EF (Mg2+ coordination), no activation by BeF3 or protein concentration above 50 microM	680826
EE370GG	Caulobacter vibrioides	Q9A3B9	mutation in active site, complete loss of catalytic activity without effect on allosteric binding of cyclic diguanylate	680703
R148A	Caulobacter vibrioides	Q9A3B9	increase in allosteric binding of cyclic diguanylate and increase in catalytic activity	680703
R148A/R178A	Caulobacter vibrioides	Q9A3B9	increase in allosteric binding of cyclic diguanylate and increase in catalytic activity	680703
R148A/R178A	Caulobacter vibrioides	-	double mutant	682885
R148A/R178A/R313A	Caulobacter vibrioides	-	triple mutant, KD for binding of cyclic di-3�,5�-guanylate: 4 microM (10fold higher than wild-type), 60fold increased KI for product inhibition by cyclic di-3�,5�-guanylate, residual catalytic activity	682885
R178A	Caulobacter vibrioides	Q9A3B9	increase in allosteric binding of cyclic diguanylate and increase in catalytic activity	680703
R313A	Caulobacter vibrioides	-	part of inhibitory site	682885
R359A	Caulobacter vibrioides	Q9A3B9	mutation in allosteric binding site of cyclic diguanylate, strong decrease in cyclic diguanylate binding, strong decrease in catalytic activity	680703
R359V	Caulobacter vibrioides	Q9A3B9	strong decrease in catalytic activity	680703
R390A	Caulobacter vibrioides	Q9A3B9	mutation in allosteric binding site of cyclic diguanylate, strong decrease in cyclic diguanylate binding. Catalytic activity comaprable to wild-type	680703
GGAAF	Pseudomonas aeruginosa	-	catalytically dead mutant of active site motif GGEEF, inactive, able to bind cyclic di-3�,5�-guanylate although nucleotide-free when purified, compact dimer-tetramer equilibrium like nucleotide-free wild-type	694796
L167D	Pseudomonas aeruginosa	-	predominantly monomeric, weakly associated dimer, purifies cyclic di-3�,5�-guanylate-bound, inactive (also upon cyclic di-3�,5�-guanylate hydrolysis)	694796
R198/242A	Pseudomonas aeruginosa	-	double mutant of inhibitory site RxxD, highly active	694796
R198A	Pseudomonas aeruginosa	-	mutant of side chain complementing the inhibitory site R242xxD, highly active, low cyclic di-3�,5�-guanylate affinity, nucleotide-free, in compact dimer-tetramer equilibrium like nucleotide-free wild-type	694796
R242A	Pseudomonas aeruginosa	-	mutant of inhibitory site RxxD, highly active, low cyclic di-3�,5�-guanylate affinity, nucleotide-free, in compact dimer-tetramer equilibrium like nucleotide-free wild-type	694796
WspGCN4-RGGDEF	Pseudomonas syringae	-	fusion protein, coiled-coil segment of GCN4 from Saccharomyces cerevisiae, C-terminal diguanylate cyclase domain with the characteristic GGDEF motif and the active site	705162
WspRD70N	Pseudomonas syringae	-	mutant, point mutation at the predicted phosphorylation site in the REC domain	705162
WspRGGDEF	Pseudomonas syringae	-	residues 172-347, C-terminal diguanylate cyclase domain with the characteristic GGDEF motif and the active site	705162
WspRstalk-GGDEF	Pseudomonas syringae	-	residues 140-347, catalytic activity is modulated by the helical stalk motif, C-terminal diguanylate cyclase domain with the characteristic GGDEF motif and the active site	705162
R158A	Thermotoga maritima	Q9X2A8	mutation of a key residue in the putative regulatory I-site, product inhibition is substantially alleviated	701669
additional information	Aliivibrio fischeri	-	enzyme disruption mutants of MifA or MifB show increased flagellin levels, while mutlicopy expression decreases them	680474
Y26A	Caulobacter vibrioides	-	almost complete loss of activity; dimerisation mutant, nearly inactive, mainly monomeric	680826
additional information	Escherichia coli	-	cells overexpressing diguanylate cyclase YddV display an abnormal cell division process when high levels of cyclic diguanylate are present. Gene yvvD is co-transcribed with dos, a heme based oxygen sensor with cyclic diguanylate phosphodiesterase activity	680795
additional information	Escherichia coli	-	a mutant, carrying an adrA mutation resulting in GGDEF -> GGAAF change in AdrA protein catalytic site, is constructed	701853
additional information	Gluconacetobacter xylinus	-	disruption of dgc genes markedly reduces in vivo cellulose production in Acetobacter xylinum	680432
L170D	Pseudomonas aeruginosa	-	highly active also in cyclic di-3�,5�-guanylate-bound state, in compact dimer-tetramer equilibrium like nucleotide-free wild-type	694796
additional information	Pseudomonas aeruginosa	-	deletion of gene PA4367 results in severe defect in swarming motility and a hyperbiofilm phenotype. Mutant exhibits increased cellular pools of cyclic di-3�,5�-guanylate, increased synthesis of a polysaccharide produced by the pel locus and decreased flagellar reversals. GGDQF and EAL domains of BifA are both required for complementation of the mutant	680510

Renatured/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

APPLICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
medicine	Escherichia coli	-	diguanylate cyclases are interesting targets for new antimicrobial agents with biofilm activity	701853
molecular biology	Pseudomonas aeruginosa	-	generation of structural models for product-inhibited, elongated dimer	694796
synthesis	Thermotoga maritima	Q9X2A8	the thermophilic enzyme is a valuable tool for c-di-GMP synthesis as well as the preparation of c-di-GMP derivatives	701669

REF.	AUTHORS	TITLE	JOURNAL	VOL.	PAGES	YEAR	ORGANISM	LINK TO PUBMED	SOURCE
679884	Ausmees, N.; Mayer, R.; Weinhouse, H.; Volman, G.; Amikam, D.; Benziman, M.; Lindberg, M.	Genetic data indicate that proteins containing the GGDEF domain possess diguanylate cyclase activity	FEMS Microbiol. Lett.	204	163-167	2001	Escherichia coli, Gluconacetobacter xylinus, Rhizobium leguminosarum	PubMed
680007	Paul, R.; Weiser, S.; Amiot, N.C.; Chan, C.; Schirmer, T.; Giese, B.; Jenal, U.	Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain	Genes Dev.	18	715-727	2004	Caulobacter vibrioides	PubMed
680432	Tal, R.; Wong, H.C.; Calhoon, R.; Gelfand, D.; Fear, A.L.; Volman, G.; Mayer, R.; Ross, P.; Amikam, D.; Weinhouse, H.; Cohen, A.; Sapir, S.; Ohana, P.; Benziman, M.	Three cdg operons control cellular turnover of cyclic di-GMP in Acetobacter xylinum: genetic organization and occurrence of conserved domains in isoenzymes	J. Bacteriol.	180	4416-4425	1998	Gluconacetobacter xylinus	PubMed
680449	Ryjenkov, D.A.; Tarutina, M.; Moskvin, O.V.; Gomelsky, M.	Cyclic diguanylate is a ubiquitous signaling molecule in bacteria: insights into biochemistry of the GGDEF protein domain	J. Bacteriol.	187	1792-1798	2005	Borrelia burgdorferi, Rhodobacter sphaeroides	PubMed
680474	O'Shea, T.M.; Klein, A.H.; Geszvain, K.; Wolfe, A.J.; Visick, K.L.	Diguanylate cyclases control magnesium-dependent motility of Vibrio fischeri	J. Bacteriol.	188	8196-8205	2006	Aliivibrio fischeri	PubMed
680510	Kuchma, S.L.; Brothers, K.M.; Merritt, J.H.; Liberati, N.T.; Ausubel, F.M.; O'Toole, G.A.	BifA, a cyclic-Di-GMP phosphodiesterase, inversely regulates biofilm formation and swarming motility by Pseudomonas aeruginosa PA14	J. Bacteriol.	189	8165-8178	2007	Pseudomonas aeruginosa	PubMed
680703	Christen, B.; Christen, M.; Paul, R.; Schmid, F.; Folcher, M.; Jenoe, P.; Meuwly, M.; Jenal, U.	Allosteric control of cyclic di-GMP signaling	J. Biol. Chem.	281	32015-32024	2006	Caulobacter vibrioides	PubMed
680795	Mendez-Ortiz, M.M.; Hyodo, M.; Hayakawa, Y.; Membrillo-Hernandez, J.	Genome-wide transcriptional profile of Escherichia coli in response to high levels of the second messenger 3', 5'-cyclic diguanylic acid. [Erratum to document cited in CA144:426702]	J. Biol. Chem.	282	22248	2007	Escherichia coli	-
680826	Paul, R.; Abel, S.; Wassmann, P.; Beck, A.; Heerklotz, H.; Jenal, U.	Activation of the diguanylate cyclase PleD by phosphorylation-mediated dimerization	J. Biol. Chem.	282	29170-29177	2007	Caulobacter vibrioides	PubMed
681997	Andrade, M.O.; Alegria, M.C.; Guzzo, C.R.; Docena, C.; Rosa, M.C.P.; Ramos, C.H.I.; Farah, C.S.	The HD-GYP domain of RpfG mediates a direct linkage between the Rpf quorum-sensing pathway and a subset of diguanylate cyclase proteins in the phytopathogen Xanthomonas axonopodis pv citri	Mol. Microbiol.	62	537-551	2006	Xanthomonas axonopodis	PubMed
682337	Ohana, P.; Delmer, D.P.; Carlson, R.W.; Glushka, J.; Azadi, P.; Bacic, T.; Benziman, M.	Identification of a novel triterpenoid saponin from Pisum sativum as a specific inhibitor of the diguanylate cyclase of Acetobacter xylinum	Plant Cell Physiol.	39	144-152	1998	Gluconacetobacter xylinus	PubMed
682338	Ohana, P.; Delmer, D.P.; Volman, G.; Benziman, M.	Glycosylated triterpenoid saponin: a specific inhibitor of diguanylate cyclase from Acetobacter xylinum. Biological activity and distribution	Plant Cell Physiol.	39	153-159	1998	Gluconacetobacter xylinus	-
682502	Chan, C.; Paul, R.; Samoray, D.; Amiot, N.C.; Giese, B.; Jenal, U.; Schirmer, T.	Structural basis of activity and allosteric control of diguanylate cyclase	Proc. Natl. Acad. Sci. USA	101	17084-17089	2004	Caulobacter vibrioides	PubMed
682885	Wassmann, P.; Chan, C.; Paul, R.; Beck, A.; Heerklotz, H.; Jenal, U.; Schirmer, T.	Structure of BeF3--modified response regulator PleD: implications for diguanylate cyclase activation, catalysis, and feedback inhibition	Structure	15	915-927	2007	Caulobacter vibrioides	PubMed
692878	Neunuebel, M.R.; Golden, J.W.	The Anabaena sp. strain PCC 7120 gene all2874 encodes a diguanylate cyclase and is required for normal heterocyst development under high-light growth conditions	J. Bacteriol.	190	6829-6836	2008	Anabaena sp.	PubMed
694796	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	601-617	2008	Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae	PubMed
701669	Rao, F.; Pasunooti, S.; Ng, Y.; Zhuo, W.; Lim, L.; Liu, A.W.; Liang, Z.X.	Enzymatic synthesis of c-di-GMP using a thermophilic diguanylate cyclase	Anal. Biochem.	389	138-142	2009	Thermotoga maritima	PubMed
701853	Antoniani, D.; Bocci, P.; Maciag, A.; Raffaelli, N.; Landini, P.	Monitoring of diguanylate cyclase activity and of cyclic-di-GMP biosynthesis by whole-cell assays suitable for high-throughput screening of biofilm inhibitors	Appl. Microbiol. Biotechnol.	85	1095-1104	2010	Escherichia coli	PubMed
702355	Tuckerman, J.R.; Gonzalez, G.; Sousa, E.H.; Wan, X.; Saito, J.A.; Alam, M.; Gilles-Gonzalez, M.A.	An oxygen-sensing diguanylate cyclase and phosphodiesterase couple for c-di-GMP control	Biochemistry	48	9764-9774	2009	Escherichia coli	PubMed
702469	Sawai, H.; Yoshioka, S.; Uchida, T.; Hyodo, M.; Hayakawa, Y.; Ishimori, K.; Aono, S.	Molecular oxygen regulates the enzymatic activity of a heme-containing diguanylate cyclase (HemDGC) for the synthesis of cyclic di-GMP	Biochim. Biophys. Acta	1804	166-172	2010	Desulfotalea psychrophila	PubMed
704312	Lai, T.H.; Kumagai, Y.; Hyodo, M.; Hayakawa, Y.; Rikihisa, Y.	The Anaplasma phagocytophilum PleC histidine kinase and PleD diguanylate cyclase two-component system and role of cyclic Di-GMP in host cell infection	J. Bacteriol.	191	693-700	2009	Anaplasma phagocytophilum	PubMed
705162	De, N.; Navarro, M.V.; Raghavan, R.V.; Sondermann, H.	Determinants for the activation and autoinhibition of the diguanylate cyclase response regulator WspR	J. Mol. Biol.	393	619-633	2009	Pseudomonas syringae	PubMed

LINKS TO OTHER DATABASES (specific for EC-Number 2.7.7.65)

NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM

IUBMB Enzyme Nomenclature

PROSITE Database of protein families and domains

SYSTERS

Protein Mutant Database

InterPro (database of protein families, domains and functional sites)

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