6GKY

Crystal structure of Coclaurine N-Methyltransferase (CNMT) bound to N-methylheliamine and SAH

Summary for 6GKY

• Entry DOI: 10.2210/pdb6gky/pdb
• Related: 6GKV
• Descriptor: Coclaurine N-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, 6,7-dimethoxy-2,4-dihydro-1~{H}-isoquinolin-3-one (3 entities in total)
• Functional Keywords: n-methylheliamine, coclaurine n-methyltransferase, transferase
• Biological source: Coptis japonica (Japanese goldthread)
• Total number of polymer chains: 2
• Total formula weight: 83324.88

Authors

Dunstan, M.S.,Levy, C.W. (deposition date: 2018-05-22, release date: 2018-06-06, Last modification date: 2025-12-10)

Primary citation

Bennett, M.R.,Thompson, M.L.,Shepherd, S.A.,Dunstan, M.S.,Herbert, A.J.,Smith, D.R.M.,Cronin, V.A.,Menon, B.R.K.,Levy, C.,Micklefield, J.
Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase.
Angew. Chem. Int. Ed. Engl., 57:10600-10604, 2018

PubMed Abstract: Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture. The specificity of CNMT was also explored with a range of natural and synthetic substrates as well as co-factor analogues. Knowledge from this study could be used to generate improved CNMT variants required to produce BIAs or synthetic derivatives.

PubMed: 29791083
DOI: 10.1002/anie.201805060

Experimental method

X-RAY DIFFRACTION (2.847 Å)