The enzyme norcoclaurine synthase (NCS) catalyzes the stereospecific Pictet-Spengler cyclization between dopamine and 4-hydroxyphenylacetaldehyde, the key step in the benzylisoquinoline alkaloid biosynthetic pathway. The crystallographic structure of norcoclaurine synthase from Thalictrum flavum in its complex with dopamine substrate and the nonreactive substrate analogue 4-hydroxybenzaldehyde has been solved at 2.1A? resolution. NCS shares no common features with the functionally correlated “Pictet-Spenglerases” that catalyze the first step of the indole alkaloids pathways and conforms to the overall fold of the Bet v1-like protein. The active site of NCS is located within a 20-A? -long catalytic tunnel and is shaped by the side chains of a tyrosine, a lysine, an aspartic, and a glutamic acid. The geometry of the amino acid 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. Site-directed mutations of the relevant residues confirm the assignment based on crystallographic findings.

Structural basis of enzymatic (S)-norcoclaurine biosynthesis / Ilari, Andrea; Franceschini, S; Bonamore, Alessandra; Arenghi, F; Botta, Bruno; Macone, Alberto; Pasquo, A; Bellucci, L; Boffi, Alberto. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 284(2):(2009), pp. 897-904. [10.1074/jbc.M803738200]

Structural basis of enzymatic (S)-norcoclaurine biosynthesis

ILARI, ANDREA;BONAMORE, ALESSANDRA;BOTTA, Bruno;MACONE, ALBERTO;BOFFI, Alberto
2009

Abstract

The enzyme norcoclaurine synthase (NCS) catalyzes the stereospecific Pictet-Spengler cyclization between dopamine and 4-hydroxyphenylacetaldehyde, the key step in the benzylisoquinoline alkaloid biosynthetic pathway. The crystallographic structure of norcoclaurine synthase from Thalictrum flavum in its complex with dopamine substrate and the nonreactive substrate analogue 4-hydroxybenzaldehyde has been solved at 2.1A? resolution. NCS shares no common features with the functionally correlated “Pictet-Spenglerases” that catalyze the first step of the indole alkaloids pathways and conforms to the overall fold of the Bet v1-like protein. The active site of NCS is located within a 20-A? -long catalytic tunnel and is shaped by the side chains of a tyrosine, a lysine, an aspartic, and a glutamic acid. The geometry of the amino acid 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. Site-directed mutations of the relevant residues confirm the assignment based on crystallographic findings.
2009
01 Pubblicazione su rivista::01a Articolo in rivista
Structural basis of enzymatic (S)-norcoclaurine biosynthesis / Ilari, Andrea; Franceschini, S; Bonamore, Alessandra; Arenghi, F; Botta, Bruno; Macone, Alberto; Pasquo, A; Bellucci, L; Boffi, Alberto. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 284(2):(2009), pp. 897-904. [10.1074/jbc.M803738200]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/229201
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