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Structures of Iridoid Synthase from Cantharanthus roseus with Bound NAD + , NADPH, or NAD + /10‐Oxogeranial: Reaction Mechanisms
- Source :
- Angewandte Chemie International Edition. 54:15478-15482
- Publication Year :
- 2015
- Publisher :
- Wiley, 2015.
-
Abstract
- Structures of the iridoid synthase nepetalactol synthase in the presence of NAD(+) , NADPH or NAD(+) /10-oxogeranial were solved. The 10-oxogeranial substrate binds in a transoid-O1-C3 conformation and can be reduced by hydride addition to form the byproduct S-10-oxo-citronellal. Tyr178 Oζ is positioned 2.5 Å from the substrate O1 and provides the second proton required for reaction. Nepetalactol product formation requires rotation about C1-C2 to form the cisoid isomer, leading to formation of the cis-enolate, together with rotation about C4-C5, which enables cyclization and lactol production. The structure is similar to that of progesterone-5β-reductase, with almost identical positioning of NADP, Lys146(147), Tyr178(179), and F342(343), but only Tyr178 and Phe342 appear to be essential for activity. The transoid 10-oxogeranial structure also serves as a model for β-face hydride attack in progesterone 5β-reductases and is of general interest in the context of asymmetric synthesis.
- Subjects :
- Models, Molecular
Iridoid
Stereochemistry
medicine.drug_class
Lactol
Acyclic Monoterpenes
Context (language use)
Article
Catalysis
Ligases
chemistry.chemical_compound
Oxidoreductase
medicine
Nepetalactol
Iridoids
chemistry.chemical_classification
Molecular Structure
ATP synthase
biology
Substrate (chemistry)
General Chemistry
NAD
Apocynaceae
chemistry
Monoterpenes
biology.protein
NAD+ kinase
NADP
Subjects
Details
- ISSN :
- 15213773 and 14337851
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie International Edition
- Accession number :
- edsair.doi.dedup.....ea783c39972a6cfa2dce572451010d28