Sandbox Reserved 1556

This is a default text for your page '. Click above on edit this page' to modify. Be careful with the < and > signs.

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

Function(s) and Biological Relevance

Benzylisoquinoline alkaloids (BIAs), plant-specialized metabolites, is the organism that forms TNMT. Tetrahydroprotoberberine N-methyltransferase catalyzes the N-methylation of (S)-stylopine in the pathway leading to protopines and benzo [c] phenanthridines. Also acts on (S)-canadine in a different pathway that leads to the production of phthalideisoquinolines. The substrate specificity of TNMT enzymes appears to arise from the arrangement of subgroup-specific stereospecific recognition elements relative to catalytic elements that are more widely-conserved.

Broader Implications

N-methylation is a recurring feature in the biosynthesis of many plant specialized metabolites, including alkaloids. A crucial step in the conserved central pathway that provides intermediates for the biosynthesis of benzylisoquinoline alkaloids (BIAs). Prominent compounds include the narcotic analgesic morphine, the cough suppressant codeine, the muscle relaxants papaverine and (+)‐tubocurarine, the anti‐microbial agent sanguinarine, and the cholesterol‐lowering drug berberine.

Structural highlights and structure-function relationships

GfTNMT was co-crystallized with the cofactor S-adenosyl-L-methionine (dmin = 1.6 A), product S-adenosyl-L-homocysteine (dmin = 1.8 A), or in complex with S-adenosyl-L-homocysteine and (S)-cis-N-methylstylopine (dmin = 1.8 A), These structures reveal for the first time how a mostly hydrophobic L-shaped substrate recognition pocket selects for the (S)-cis configuration of the two central six-membered rings in protoberberine BIA compounds. The substrate specificity of TNMT enzymes appears to arise from the arrangement of subgroup-specific stereospecific recognition elements relative to catalytic elements that are more widely conserved among all BIA NMTs. The binding mode of protoberberine compounds to GfTNMT appears to be similar to coclaurine NMT, with the isoquinoline rings buried deepest in the binding pocket. This binding mode differs from that of pavine NMT, in which the benzyl ring is bound more deeply than the isoquinoline rings. The insights into substrate recognition and catalysis provided here form a sound basis for the rational engineering of NMT enzymes for chemoenzymatic synthesis and metabolic engineering.

Energy Transformation

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.