Pubblication 2 J. Biol. Chem (2009) Jan 9;284(2):897-904

Structural basis of enzymatic S-norcoclaurine biosynthesis

The enzyme S-norcoclaurine synthase (SNCS) catalyzes the stereoselective Pictet-Spengler cyclization between dopamine and 4-hydroxyphenylacetaldehyde, the key step in benzylisoquinoline alkaloids biosynthetic pathway. The crystallographic structure of S-norcoclaurine synthase from Thalictrum flavum in its complex with dopamine substrate and the non-reactive substrate analogue 4-hydroxybenzaldehyde has been solved at 2.1-Å resolution. SNCS shares no common features with the functionally correlated “Pictet-Spenglerases” that catalyzes the first step of the indole alkaloids pathways and conforms to the overall fold of the Bet v1-like protein. The active site of SNCS is located within a 20 Å long catalytic tunnel and is shaped by the side chains of a tyrosine, a lysin, an aspartic and a glutammic acid. The geometry of the aminoacid side chains with respect to the substrates reveals the structural determinants that govern the mechanism of the stereoselective Pictet-Spengler cyclization thus establishing an excellent foundation for the understanding of the finer details of the catalytic process. Figure: Overall structure of S-norcoclaurine synthase (SNCS) from Thalictrum flavum. The ribbon structure refers to the SNCS monomer. The substrates 4-hydroxyphenylacetaldehyde and dopamine are depicted (right side) together with the s-norcoclaurine product (left side).