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Literature summary for 3.2.2.9 extracted from

  • Gutierrez, J.A.; Crowder, T.; Rinaldo-Matthis, A.; Ho, M.C.; Almo, S.C.; Schramm, V.L.
    Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing (2009), Nat. Chem. Biol., 5, 251-257.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development potential of MTAN as target for bacterial anti-infective drug design Vibrio cholerae serotype O1

Cloned(Commentary)

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 (Commentary)

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

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 [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

Organism UniProt Comment Textmining
Vibrio cholerae serotype O1
-
-
-
Vibrio cholerae serotype O1 N16961
-
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Vibrio cholerae serotype O1

Substrates and Products (Substrate)

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

Subunits Comment Organism
dimer crystallography Vibrio cholerae serotype O1

Synonyms

Synonyms Comment Organism
5'-methylthioadenosine nucleosidase
-
Vibrio cholerae serotype O1
MTAN
-
Vibrio cholerae serotype O1

Turnover Number [1/s]

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 [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 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 [mM/s]

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