Application | Comment | Organism |
---|---|---|
drug development | potential of MTAN as target for bacterial anti-infective drug design | Vibrio cholerae serotype O1 |
Cloned (Comment) | Organism |
---|---|
expressed in Escherichia coli as a His-tagged recombinant protein | Vibrio cholerae serotype O1 |
expressed in Escherichia coli as His-tagged protein | Vibrio cholerae serotype O1 |
Crystallization (Comment) | Organism |
---|---|
5'-butylthio-DADMe-immucillinA-MTAN complex, by sitting drop vapor diffusion, at 18°C, to 2.3 A resolution. Structure of the MTAN monomer is a single mixed alpha/beta domain with central twisted nine-stranded mixed beta-sheet surrounded by six alpha-helices. Catalytic site is situated in a pocket formed by residues from beta10, a loop between beta8 and alpha4 and a loop contributed by the adjacent subunit. The catalytic site consists of the base binding site, the ribose binding site and the 5'-alkylthio-binding site | Vibrio cholerae serotype O1 |
in complex with But-dadme-imma A, sitting drop vapour diffusion method, with 0.2 M potassium iodide and 20% (w/v) PEG3350 | Vibrio cholerae serotype O1 |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
5'-butylthio-DADMe-ImmucillinA | potent MTAN inhibitor, disrupting autoinducer production in a dose-dependent manner without affecting growth. Despite having a 3fold lower affinity with purified MTAN, 5'-butylthio-DADMe-ImmucillinA inhibits cellular MTAN activity 5fold better than its methylthio- and ethylthio-counterparts, significant diffusion barrier | Vibrio cholerae serotype O1 | |
5'-ethylthio-DADMe-ImmucillinA | potent MTAN inhibitor, disrupting autoinducer production in a dose-dependent manner without affecting growth | Vibrio cholerae serotype O1 | |
5'-methylthio-DADMe-ImmucillinA | potent MTAN inhibitor, disrupting autoinducer production in a dose-dependent manner without affecting growth | Vibrio cholerae serotype O1 | |
benzylthio-immucillin A | - |
Vibrio cholerae serotype O1 | |
butylthio-4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-A | picomolar inhibitor of MTAN | Vibrio cholerae serotype O1 | |
ethylthio-4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-A | picomolar inhibitor of MTAN | Vibrio cholerae serotype O1 | |
ethylthio-immucillin A | - |
Vibrio cholerae serotype O1 | |
methylthio-4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-A | picomolar inhibitor of MTAN | Vibrio cholerae serotype O1 | |
methylthio-immucillin A | - |
Vibrio cholerae serotype O1 | |
p-chlorophenylthio-immucillin A | - |
Vibrio cholerae serotype O1 |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.003 | - |
5'-methylthioadenosine | at 25°C, in 100 mM HEPES buffer, pH 7.5, 50 mM KCl | Vibrio cholerae serotype O1 | |
0.024 | - |
S-adenosyl-L-homocysteine | at 25°C, in 100 mM HEPES, pH 7.5, and 50 mM KCl | Vibrio cholerae serotype O1 | |
0.024 | - |
S-adenosylhomocysteine | at 25°C, in 100 mM HEPES buffer, pH 7.5, 50 mM KCl | Vibrio cholerae serotype O1 |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Vibrio cholerae serotype O1 | - |
- |
- |
Vibrio cholerae serotype O1 N16961 | - |
- |
- |
Purification (Comment) | Organism |
---|---|
- |
Vibrio cholerae serotype O1 |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
5'-methylthioadenosine + phosphate | - |
Vibrio cholerae serotype O1 | adenine + 5-methylthio-D-ribose 1-phosphate | - |
? | |
5'-methylthioadenosine + phosphate | - |
Vibrio cholerae serotype O1 N16961 | adenine + 5-methylthio-D-ribose 1-phosphate | - |
? | |
S-adenosyl-L-homocysteine + H2O | - |
Vibrio cholerae serotype O1 | adenine + S-ribosyl-L-homocysteine | - |
? | |
S-adenosyl-L-homocysteine + H2O | - |
Vibrio cholerae serotype O1 N16961 | adenine + S-ribosyl-L-homocysteine | - |
? | |
S-adenosylhomocysteine + ? | - |
Vibrio cholerae serotype O1 | ? | - |
? | |
S-adenosylhomocysteine + ? | - |
Vibrio cholerae serotype O1 N16961 | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | crystallography | Vibrio cholerae serotype O1 |
Synonyms | Comment | Organism |
---|---|---|
5'-methylthioadenosine nucleosidase | - |
Vibrio cholerae serotype O1 |
MTAN | - |
Vibrio cholerae serotype O1 |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.5 | - |
S-adenosyl-L-homocysteine | at 25°C, in 100 mM HEPES, pH 7.5, and 50 mM KCl | Vibrio cholerae serotype O1 | |
0.5 | - |
S-adenosylhomocysteine | at 25°C, in 100 mM HEPES buffer, pH 7.5, 50 mM KCl | Vibrio cholerae serotype O1 | |
2 | - |
5'-methylthioadenosine | at 25°C, in 100 mM HEPES buffer, pH 7.5, 50 mM KCl | Vibrio cholerae serotype O1 |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00000007 | - |
ethylthio-4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-A | at 25°C, in 50 mM phosphate buffer, pH 7.9, and 10 mM KCl | Vibrio cholerae serotype O1 | |
0.00000007 | - |
5'-ethylthio-DADMe-ImmucillinA | in 50 mM phosphate buffer, pH 7.9, 10 mM KCl, at 25°C | Vibrio cholerae serotype O1 | |
0.000000073 | - |
methylthio-4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-A | at 25°C, in 50 mM phosphate buffer, pH 7.9, and 10 mM KCl | Vibrio cholerae serotype O1 | |
0.000000073 | - |
5'-methylthio-DADMe-ImmucillinA | in 50 mM phosphate buffer, pH 7.9, 10 mM KCl, at 25°C | Vibrio cholerae serotype O1 | |
0.000000208 | - |
butylthio-4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-A | at 25°C, in 50 mM phosphate buffer, pH 7.9, and 10 mM KCl | Vibrio cholerae serotype O1 | |
0.000000208 | - |
5'-butylthio-DADMe-ImmucillinA | in 50 mM phosphate buffer, pH 7.9, 10 mM KCl, at 25°C | Vibrio cholerae serotype O1 |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.000006 | - |
at 25°C, in 50 mM phosphate buffer, pH 7.9, and 10 mM KCl | Vibrio cholerae serotype O1 | butylthio-4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-A | |
0.000006 | - |
in 50 mM phosphate buffer, pH 7.9, 10 mM KCl, at 25°C | Vibrio cholerae serotype O1 | 5'-butylthio-DADMe-ImmucillinA | |
0.000027 | - |
at 25°C, in 50 mM phosphate buffer, pH 7.9, and 10 mM KCl | Vibrio cholerae serotype O1 | methylthio-4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-A | |
0.000027 | - |
in 50 mM phosphate buffer, pH 7.9, 10 mM KCl, at 25°C | Vibrio cholerae serotype O1 | 5'-methylthio-DADMe-ImmucillinA | |
0.000031 | - |
at 25°C, in 50 mM phosphate buffer, pH 7.9, and 10 mM KCl | Vibrio cholerae serotype O1 | ethylthio-4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-A | |
0.000031 | - |
in 50 mM phosphate buffer, pH 7.9, 10 mM KCl, at 25°C | Vibrio cholerae serotype O1 | 5'-ethylthio-DADMe-ImmucillinA |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
660 | - |
5'-methylthioadenosine | at 25°C, in 100 mM HEPES buffer, pH 7.5, 50 mM KCl | Vibrio cholerae serotype O1 |