5dbf

Publication Abstract from PubMed

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 Ozeta is positioned 2.5 A 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-5beta-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 beta-face hydride attack in progesterone 5beta-reductases and is of general interest in the context of asymmetric synthesis.

Structures of Iridoid Synthase from Cantharanthus roseus with Bound NAD(+) , NADPH, or NAD(+) /10-Oxogeranial: Reaction Mechanisms.,Hu Y, Liu W, Malwal SR, Zheng Y, Feng X, Ko TP, Chen CC, Xu Z, Liu M, Han X, Gao J, Oldfield E, Guo RT Angew Chem Int Ed Engl. 2015 Dec 14;54(51):15478-82. doi: 10.1002/anie.201508310., Epub 2015 Nov 13. PMID:26768532^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.