6F9Q

Binary complex of a 7S-cis-cis-nepetalactol cyclase from Nepeta mussinii with NAD+

Summary for 6F9Q

• Entry DOI: 10.2210/pdb6f9q/pdb
• Descriptor: 7S-cis-cis-nepetalactol cyclase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: iridoid, natural product, biosynthesis, short chain dehydrogenase, cyclase, biosynthetic protein
• Biological source: Nepeta racemosa
• Total number of polymer chains: 4
• Total formula weight: 116246.40

Authors

Lichman, B.R.,Kamileen, M.O.,Titchiner, G.,Saalbach, G.,Stevenson, C.E.M.,Lawson, D.M.,O'Connor, S.E. (deposition date: 2017-12-15, release date: 2018-12-12, Last modification date: 2024-01-17)

Primary citation

Lichman, B.R.,Kamileen, M.O.,Titchiner, G.R.,Saalbach, G.,Stevenson, C.E.M.,Lawson, D.M.,O'Connor, S.E.
Uncoupled activation and cyclization in catmint reductive terpenoid biosynthesis.
Nat. Chem. Biol., 15:71-79, 2019

PubMed Abstract: Terpene synthases typically form complex molecular scaffolds by concerted activation and cyclization of linear starting materials in a single enzyme active site. Here we show that iridoid synthase, an atypical reductive terpene synthase, catalyzes the activation of its substrate 8-oxogeranial into a reactive enol intermediate, but does not catalyze the subsequent cyclization into nepetalactol. This discovery led us to identify a class of nepetalactol-related short-chain dehydrogenase enzymes (NEPS) from catmint (Nepeta mussinii) that capture this reactive intermediate and catalyze the stereoselective cyclisation into distinct nepetalactol stereoisomers. Subsequent oxidation of nepetalactols by NEPS1 provides nepetalactones, metabolites that are well known for both insect-repellent activity and euphoric effects in cats. Structural characterization of the NEPS3 cyclase reveals that it binds to NAD yet does not utilize it chemically for a non-oxidoreductive formal [4 + 2] cyclization. These discoveries will complement metabolic reconstructions of iridoid and monoterpene indole alkaloid biosynthesis.

PubMed: 30531909
DOI: 10.1038/s41589-018-0185-2

Experimental method

X-RAY DIFFRACTION (1.4 Å)