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Literature summary for 2.7.7.65 extracted from

  • Fernicola, S.; Paiardini, A.; Giardina, G.; Rampioni, G.; Leoni, L.; CutruzzolÃxa0, F.; Rinaldo, S.
    In silico discovery and in vitro validation of catechol-containing sulfonohydrazide compounds as potent inhibitors of the diguanylate cyclase PleD (2016), J. Bacteriol., 198, 147-156 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.7.65

Activating Compound

Activating Compound Comment Organism Structure
4-(5-[(E)-[2-(4-amino-1,2,5-oxadiazole-3-carbonyl)hydrazinylidene]methyl]furan-2-yl)benzoic acid 18% activation at 0.1 mM Caulobacter vibrioides
4-chloro-N'-[(E)-(4-cyanophenyl)methylidene]-3-nitrobenzene-1-sulfonohydrazide 15% activation at 0.1 mM Caulobacter vibrioides
4-[(E)-[2-(4-hydroxy-6-methylpyrimidin-2-yl)hydrazinylidene]methyl]phenyl 3-nitrobenzoate 8% activation at 0.1 mM Caulobacter vibrioides
4-[(E)-[2-(4-sulfamoylphenyl)hydrazinylidene]methyl]benzoic acid 6% activation at 0.1 mM Caulobacter vibrioides
additional information PleD contains an extra metal binding site or beryllium metal for activation Caulobacter vibrioides
N'-[(E)-(4-chloro-3-nitrophenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide 3% activation at 0.1 mM Caulobacter vibrioides
N'-[(E)-(4-cyanophenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide 4% activation at 0.1 mM Caulobacter vibrioides

Inhibitors

Inhibitors Comment Organism Structure
2-(5-amino-1,3,4-thiadiazol-2-yl)-N'-[(1E,2E)-3-(3-nitrophenyl)prop-2-en-1-ylidene]acetohydrazide 4% inhibition at 0.1 mM Caulobacter vibrioides
3-(3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-yl)-N'-[(E)-(4-nitrophenyl)methylidene]propanehydrazide 11.0% inhibition at 0.1 mM Caulobacter vibrioides
3-nitro-N'-[(E)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1-sulfonohydrazide 85% inhibition at 0.1 mM, competitive binding Caulobacter vibrioides
3-nitro-N'-[(E)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1-sulfonohydrazide
-
 Pseudomonas aeruginosa
additional information virtual screening of the ZINC database, in silico discovery and in vitro validation of catechol-containing sulfonohydrazide compounds as potent inhibitors of the diguanylate cyclase PleD. The compounds retrieved from the pharmacophore searches are docked into the active site of PleD, by means of Molegro Virtual Docker (MVD) software (CLCbio), using the three-dimensional structure of PleD (PDB ID 2V0N). Binding of N'-[(E)-(3,4-dihydroxyphenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide and 3-nitro-N'-[(E)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1-sulfonohydrazide to PleD is stabilized by polar interactions with residues surrounding the GTP binding pocket, namely, N335, D344, and R366. N'-[(E)-(3,4-dihydroxyphenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide and 3-nitro-N'-[(E)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1-sulfonohydrazide share a hydrazine moiety with the previously identified inhibitors LP3134 and LP4010, which has been predicted to interact with the amino group of N335 Caulobacter vibrioides
additional information virtual screening of the ZINC database, in silico discovery and in vitro validation of catechol-containing sulfonohydrazide compounds as potent inhibitors of the diguanylate cyclase PleD. N'-[(E)-(3,4-dihydroxyphenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide and 3-nitro-N'-[(E)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1-sulfonohydrazide are also tested on the YfiNHAMP-GGDEF and WspR DGCs from Pseudomonas aeruginosa, two DGCs which are in the on state and therefore do not require preactivation; virtual screening of the ZINC database, in silico discovery and in vitro validation of catechol-containing sulfonohydrazide compounds as potent inhibitors of the diguanylate cyclase PleD. N'-[(E)-(3,4-dihydroxyphenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide and 3-nitro-N'-[(E)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1-sulfonohydrazide are also tested on the YfiNHAMP-GGDEF and WspR DGCs from Pseudomonas aeruginosa, two DGCs which are in the on state and therefore do not require preactivation Pseudomonas aeruginosa
N'-[(E)-(2,4-dihydroxyphenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide 17% inhibition at 0.1 mM; 6% inhibition at 0.1 mM Caulobacter vibrioides
N'-[(E)-(2-hydroxyphenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide 13% inhibition at 0.1 mM Caulobacter vibrioides
N'-[(E)-(3,4-dihydroxyphenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide 83.4% inhibition at 0.1 mM, competitive binding Caulobacter vibrioides
N'-[(E)-(3,4-dihydroxyphenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide
-
 Pseudomonas aeruginosa

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Caulobacter vibrioides
Mg2+ required Pseudomonas aeruginosa
additional information PleD contains an extra metal binding site or beryllium metal for activation Caulobacter vibrioides

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2 GTP Caulobacter vibrioides
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Pseudomonas aeruginosa
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Pseudomonas aeruginosa ATCC 15692
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Caulobacter vibrioides ATCC 19089
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Pseudomonas aeruginosa 1C
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Caulobacter vibrioides CB15
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Pseudomonas aeruginosa PRS 101
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Pseudomonas aeruginosa DSM 22644
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Pseudomonas aeruginosa CIP 104116
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Pseudomonas aeruginosa LMG 12228
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP Pseudomonas aeruginosa JCM 14847
-
 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?

Organism

Organism UniProt Comment Textmining
Caulobacter vibrioides Q9A5I5 Caulobacter crescentus
-
Caulobacter vibrioides ATCC 19089 Q9A5I5 Caulobacter crescentus
-
Caulobacter vibrioides CB15 Q9A5I5 Caulobacter crescentus
-
Pseudomonas aeruginosa A0A0C7ADU5
-
-
Pseudomonas aeruginosa Q9HXT9
-
-
Pseudomonas aeruginosa 1C Q9HXT9
-
-
Pseudomonas aeruginosa ATCC 15692 Q9HXT9
-
-
Pseudomonas aeruginosa CIP 104116 Q9HXT9
-
-
Pseudomonas aeruginosa DSM 22644 Q9HXT9
-
-
Pseudomonas aeruginosa JCM 14847 Q9HXT9
-
-
Pseudomonas aeruginosa LMG 12228 Q9HXT9
-
-
Pseudomonas aeruginosa PRS 101 Q9HXT9
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2 GTP
-
 Caulobacter vibrioides 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Pseudomonas aeruginosa 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Pseudomonas aeruginosa ATCC 15692 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Caulobacter vibrioides ATCC 19089 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Pseudomonas aeruginosa 1C 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Caulobacter vibrioides CB15 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Pseudomonas aeruginosa PRS 101 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Pseudomonas aeruginosa DSM 22644 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Pseudomonas aeruginosa CIP 104116 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Pseudomonas aeruginosa LMG 12228 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?
2 GTP
-
 Pseudomonas aeruginosa JCM 14847 2 diphosphate + cyclic di-3',5'-guanylate
-
 ?

Synonyms

Synonyms Comment Organism
DGC
-
 Caulobacter vibrioides
DGC
-
 Pseudomonas aeruginosa
PleD
-
 Caulobacter vibrioides
WspR
-
 Pseudomonas aeruginosa
YfiN
-
 Pseudomonas aeruginosa
YfiNHAMP-GGDEF
-
 Pseudomonas aeruginosa

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
22
-
 assay at room temperature Caulobacter vibrioides
22
-
 assay at room temperature Pseudomonas aeruginosa

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Caulobacter vibrioides
7.5
-
 assay at Pseudomonas aeruginosa

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.01105
-
 pH 7.5, 22°C Caulobacter vibrioides N'-[(E)-(3,4-dihydroxyphenyl)methylidene]-4-methyl-3-nitrobenzene-1-sulfonohydrazide
0.01107
-
 pH 7.5, 22°C Caulobacter vibrioides 3-nitro-N'-[(E)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1-sulfonohydrazide

General Information

General Information Comment Organism
additional information binding mode of the substrate analogue GTP-alpha-S (guanosine-alpha-thio-triphosphate) bound to PleD Caulobacter vibrioides
additional information binding mode of the substrate analogue GTP-alpha-S (guanosine-alpha-thio-triphosphate) bound to PleD Pseudomonas aeruginosa