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Literature summary for 3.3.2.8 extracted from

  • Rinaldi, S.; Van Der Kamp, M.; Ranaghan, K.; Mulholland, A.; Colombo, G.
    Understanding complex mechanisms of enzyme reactivity the case of limonene-1,2-epoxide hydrolases (2018), ACS Catal., 8, 5698-5707 .
No PubMed abstract available
Search for more literature for 3.3.2.8

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
limonene-1,2-epoxide + H2O Rhodococcus erythropolis
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 limonene-1,2-diol
-
 ?
limonene-1,2-epoxide + H2O Rhodococcus erythropolis DCL14
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 limonene-1,2-diol
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 ?

Organism

Organism UniProt Comment Textmining
Rhodococcus erythropolis Q9ZAG3
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-
Rhodococcus erythropolis DCL14 Q9ZAG3
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-

Reaction

Reaction Comment Organism Reaction ID
1,2-epoxymenth-8-ene + H2O = menth-8-ene-1,2-diol catalytic mechanism, quantum mechanics/molecular mechanics (QM/MM) free energy calculations for the reaction with molecular dynamics simulations Rhodococcus erythropolis
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
cyclohexene-1,2-epoxide + H2O 0.25% activity compared to limonene-1,2-epoxide Rhodococcus erythropolis cyclohexane-1,2-diol
-
 ?
cyclohexene-1,2-epoxide + H2O 0.25% activity compared to limonene-1,2-epoxide Rhodococcus erythropolis DCL14 cyclohexane-1,2-diol
-
 ?
limonene-1,2-epoxide + H2O
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 Rhodococcus erythropolis limonene-1,2-diol
-
 ?
limonene-1,2-epoxide + H2O
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 Rhodococcus erythropolis DCL14 limonene-1,2-diol
-
 ?

Subunits

Subunits Comment Organism
dimer LEH forms a stable homodimer, and each monomer can bind a substrate molecule within its catalytic pocket Rhodococcus erythropolis

Synonyms

Synonyms Comment Organism
LEH
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 Rhodococcus erythropolis

General Information

General Information Comment Organism
additional information quantum mechanics/molecular mechanics (QM/MM) free energy calculations for the reaction with molecular dynamics simulations of the enzyme internal dynamics, and the calculation of binding affinities (using the WaterSwap method) for various representatives of the enzyme conformational ensemble, show that the presence of natural or non-natural substrates differentially modulates the dynamic and catalytic behavior of LEH. The cross-talk between the protein and the ligands favors the selection of specific substrate-dependent interactions in the binding site, priming reactive complexes to select different preferential reaction pathways. LEH substrate binding pocket structure, LEH forms a stable homodimer, and each monomer can bind a substrate molecule within its catalytic pocket, overview. Crucial role of monomer-monomer interactions in stabilizing and tuning LEH dynamics and stability. Hydrolysis by LEH occurs via a complex mechanism, the Asp101-Arg99-Asp132 triad drives a concerted reaction involving the deprotonation of a water molecule by Asp132, the nucleophilic attack of the resulting hydroxide ion on the epoxide and protonation of the oxirane ring by the protonated Asp101 (specifically labeled Ash101). Arg99 is strongly associated through hydrogen bonds and electrostatic interactions with both Asp101 and Asp132 and even if it is not directly involved in the reaction mechanism, its mutation results in a deactivated enzyme. This complex picture is completed by the proper positioning and activation of the nucleophilic water by the H-bond network formed by Asn55 and Tyr53 (and Asp132 itself). In the model, the side chains of the residues of the catalytic triad, the water molecule and the epoxide are included in the QM region. The opening of the epoxide can result from the attack on either of the two carbon atoms of the LEO oxirane ring. Experimental evidence indicates that the water molecule privileges the attack on the more substituted C1 atom Rhodococcus erythropolis
physiological function limonene-1,2-epoxide hydrolases (LEHs), a subset of the epoxide hydrolase family, present interesting opportunities for the mild, regio- and stereo- selective hydrolysis of epoxide substrates. LEHs show moderate enantioselectivity for non-natural ligands, combined with narrow substrate specificity Rhodococcus erythropolis