5DBG

Crystal Structure of Iridoid Synthase from Cantharanthus roseus in complex with NAD+

Summary for 5DBG

• Entry DOI: 10.2210/pdb5dbg/pdb
• Related: 5DBF 5DBI
• Descriptor: Iridoid synthase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• Functional Keywords: metal-binding, substrate binding, acidocalcisomal pyrophosphatase, inhibitor, oxidoreductase
• Biological source: Catharanthus roseus (Madagascar periwinkle)
• Cellular location: Cytoplasm, cytosol : K7WDL7
• Total number of polymer chains: 2
• Total formula weight: 85893.69

Authors

Liu, W.D.,Hu, Y.M.,Zheng, Y.Y.,Xu, Z.X.,Ko, T.P.,Chen, C.C.,Guo, R.T. (deposition date: 2015-08-21, release date: 2015-11-04, Last modification date: 2023-11-08)

Primary citation

Hu, Y.M.,Liu, W.D.,Malwal, S.R.,Zheng, Y.Y.,Feng, X.X.,Ko, T.P.,Chen, C.C.,Xu, Z.X.,Liu, M.X.,Han, X.,Gao, J.,Oldfield, E.,Guo, R.T.
Structures of Iridoid Synthase from Cantharanthus roseus with Bound NAD(+) , NADPH, or NAD(+) /10-Oxogeranial: Reaction Mechanisms
Angew.Chem.Int.Ed.Engl., 54:15478-15482, 2015

PubMed 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.

PubMed: 26768532
DOI: 10.1002/anie.201508310

Experimental method

X-RAY DIFFRACTION (1.95 Å)