EC Number   |
General Information |
Reference |
|---|
    1.5.1.27 | evolution |
the enzyme belongs to the aldo-keto reductase family |
743843 |
| 1.5.1.27 | evolution |
with respect to functionally characterized AKRs, several unique substitutions are observed in DRR including the replacement of His119 with Pro and the replacement of Lys86 with Met (numbering as in COR). The lack of titratable protons in the active site side chains Pro698 and Met665 (corresponding to His119 and Lys86 in COR respectively) indicates that the proton transfer steps in the canonical AKR mechanism cannot occur in DRR. Comparison of DRR with COR and members of the steroid reductase AKR subfamily, including the extensively investigated enzyme AKR1D1 (human steroid 5beta-reductase), which catalyzes the stereospecific NADPH-dependent reduction of the C4-C5 double bond of bile acid intermediates and steroid hormones, suggests that DRR may employ a partially analogous catalytic mechanism. Analysis of the significance of molecular evolution events in the COR/DRR lineage and highlighting the possibility of analogous catalytic mechanisms having evolved independently in two very distinct lineages, overview |
765081 |
| 1.5.1.27 | metabolism |
in opium poppy, the first committed step in morphine biosynthesis is the stereochemical inversion of (S)-reticuline to (R)-reticuline by reticuline epimerase (REPI). DRR homology model, overview |
765081 |
| 1.5.1.27 | more |
analysis of the molecular basis of substrate recognition in codeinone reductase (COR) catalyzing the final and penultimate steps in the biosynthesis of codeine and morphine, respectively, in opium poppy, and the closely related 1,2-dehydroreticuline reductase responsible for the second half of a stereochemical inversion that initiates the morphine biosynthesis pathway. The elucidation of the COR crystal structure allows the generation of more reliable homology models for 1,2-dehydroreticuline reductase (DRR, 72% amino acid identity), the only other known aldo-keto reductase (AKR) involved in benzylisoquinoline alkaloids (BIAs) biosynthesis |
765081 |
| 1.5.1.27 | physiological function |
direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. The P450 module of the bifunctional enzyme is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirms that these two modules are contained on a single polypeptide in vivo |
743843 |
| 1.5.1.27 | physiological function |
DRR is the aldo-keto reductase (AKR) domain of the reticuline epimerase (REPI) fusion enzyme, in which a cytochrome P450 domain first oxidizes (S)-reticuline to 1,2-dehydroreticuline, and then DRR catalyzes a stereospecific reduction of the C=N double bond in 1,2-dehydroreticuline to (R)-reticuline |
765081 |
