| Structure Identification: |
| J Biol Chem. 2012 Mar 30;287(14):11213-21. | | Crystal structure of perakine reductase, founding member of a novel aldo-keto reductase (AKR) subfamily that undergoes unique conformational changes during NADPH binding.[Pubmed: 22334702] |
METHODS AND RESULTS:
Perakine reductase (PR) catalyzes the NADPH-dependent reduction of the aldehyde Perakine to yield the alcohol raucaffrinoline in the biosynthetic pathway of ajmaline in Rauvolfia, a key step in indole alkaloid biosynthesis. Sequence alignment shows that PR is the founder of the new AKR13D subfamily and is designated AKR13D1. The x-ray structure of methylated His(6)-PR was solved to 2.31 Å. However, the active site of PR was blocked by the connected parts of the neighbor symmetric molecule in the crystal. To break the interactions and obtain the enzyme-ligand complexes, the A213W mutant was generated. The atomic structure of His(6)-PR-A213W complex with NADPH was determined at 1.77 Å.
CONCLUSIONS:
Overall, PR folds in an unusual α(8)/β(6) barrel that has not been observed in any other AKR protein to date. NADPH binds in an extended pocket, but the nicotinamide riboside moiety is disordered. Upon NADPH binding, dramatic conformational changes and movements were observed: two additional β-strands in the C terminus become ordered to form one α-helix, and a movement of up to 24 Å occurs. This conformational change creates a large space that allows the binding of substrates of variable size for PR and enhances the enzyme activity; as a result cooperative kinetics are observed as NADPH is varied. As the founding member of the new AKR13D subfamily, PR also provides a structural template and model of cofactor binding for the AKR13 family. | | Natural Product Research & Development,2007,19 (10) :235-239. | | Indole Alkaloids from Rauwolfia vomitoria[Reference: WebLink] | Fifteen indole alkaloids were isolated from the roots of Rauwolfia vomitoria.
METHODS AND RESULTS:
On the basis of spectroscopic evidence, their structures were identified as reserpine (1), tetrahydroalstonine (2), isosandwicine (3), methyl reserpate (4) ,ajmaline (5) , sandwicine (6) ,isorauhimbine (7) , Perakine (8) , α-yohimbine (9) , yohimbine (10) , mitoridine (11) ,tetraphyllicine (12), harman (13) ,mauiensine (14), and 12-hydroxymauiensine (15). Compounds 13 aˆ¼ 15 were isolated from this plant for the first time. |
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