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Literature summary for 3.1.1.1 extracted from

  • Liu, P.; Ewis, H.E.; Tai, P.C.; Lu, C.D.; Weber, I.T.
    Crystal structure of the Geobacillus stearothermophilus carboxylesterase Est55 and its activation of prodrug CPT-11 (2007), J. Mol. Biol., 367, 212-223.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.1.1.1

Application

Application Comment Organism
medicine enzyme can activate prodrug 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin to give 7-ethyl-10-hydroxycampothecin, i.e. SN-38, a topoisomerase inhibitor used in cancer therapy Geobacillus stearothermophilus

Crystallization (Commentary)

Crystallization (Comment) Organism
at 2.0 and 1.58 A resolution. Enzyme folds into a catalytic domain, an alpha/beta domain and a regulatory domain. Residue C408 adjacent to the active site is triply oxidized and may have a regulatory role Geobacillus stearothermophilus

Protein Variants

Protein Variants Comment Organism
C408A kinetics similar to wild-type Geobacillus stearothermophilus
C408G 4fold decrease in kcat value Geobacillus stearothermophilus
C408P kinetics similar to wild-type Geobacillus stearothermophilus
C408S 4fold increase in Km value Geobacillus stearothermophilus
C408V kinetics similar to wild-type Geobacillus stearothermophilus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0186
-
 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin wild-type, pH 8.5 Geobacillus stearothermophilus
0.0206
-
 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin mutant C408P, pH 8.5 Geobacillus stearothermophilus
0.0223
-
 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin mutant C408V, pH 8.5 Geobacillus stearothermophilus
0.0224
-
 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin mutant C408G, pH 8.5 Geobacillus stearothermophilus
0.0231
-
 4-nitrophenyl butanoate mutant C408G, pH 8.5 Geobacillus stearothermophilus
0.0242
-
 4-nitrophenyl butanoate wild-type, pH 8.5 Geobacillus stearothermophilus
0.026
-
 4-nitrophenyl butanoate mutant C408P, pH 8.5 Geobacillus stearothermophilus
0.0283
-
 4-nitrophenyl butanoate mutant C408V, pH 8.5 Geobacillus stearothermophilus
0.0328
-
 4-nitrophenyl butanoate mutant C408A, pH 8.5 Geobacillus stearothermophilus
0.0453
-
 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin mutant C408A, pH 8.5 Geobacillus stearothermophilus
0.0971
-
 4-nitrophenyl butanoate mutant C408S, pH 8.5 Geobacillus stearothermophilus

Organism

Organism UniProt Comment Textmining
Geobacillus stearothermophilus
-
 isoform Est55
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4-nitrophenyl butanoate + H2O
-
 Geobacillus stearothermophilus 4-nitrophenol + butanoate
-
 ?
7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin + H2O i.e. irinotecan, CPT-11, prodrug Geobacillus stearothermophilus 7-ethyl-10-hydroxycampothecin + ? i.e. SN-38, topoisomerase inhibitor used in cancer therapy ?

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.000022
-
 4-nitrophenyl butanoate mutant C408G, pH 8.5 Geobacillus stearothermophilus
0.000065
-
 4-nitrophenyl butanoate mutant C408P, pH 8.5 Geobacillus stearothermophilus
0.000079
-
 4-nitrophenyl butanoate wild-type, pH 8.5 Geobacillus stearothermophilus
0.000107
-
 4-nitrophenyl butanoate mutant C408V, pH 8.5 Geobacillus stearothermophilus
0.000127
-
 4-nitrophenyl butanoate mutant C408S, pH 8.5 Geobacillus stearothermophilus
0.000137
-
 4-nitrophenyl butanoate mutant C408A, pH 8.5 Geobacillus stearothermophilus