Structural highlights
Function[PERR_RAUSE] Aldo-keto reductase involved in the biosynthesis of monoterpenoid indole alkaloids. Broad substrate specificity enzyme with a high selectivity in the group of alkaloids. Can use perakine, 19(S),20(R)-dihydro-peraksine-17,21-al, cinnamic aldehyde, p-coumaric aldehyde and 3-(3,4,5-trimethoxyphenyl)propanal as substrates, but not ketosteroids such as progesterone. NADPH could not be replaced by NADH.[1] Publication Abstract from PubMedPerakine 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 A. 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 A. Overall, PR folds in an unusual alpha(8)/beta(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 beta-strands in the C terminus become ordered to form one alpha-helix, and a movement of up to 24 A 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. Crystal structure of perakine reductase, founding member of a novel aldo-keto reductase (AKR) subfamily that undergoes unique conformational changes during NADPH binding.,Sun L, Chen Y, Rajendran C, Mueller U, Panjikar S, Wang M, Mindnich R, Rosenthal C, Penning TM, Stockigt J J Biol Chem. 2012 Mar 30;287(14):11213-21. Epub 2012 Feb 13. PMID:22334702[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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