InterPro domain: IPR004298

Nicotianamine synthase 2.5.1.43 catalyzes the trimerization of S-adenosylmethionine to yield one molecule of nicotianamine. Nicotianamine has an important role in plant iron uptake mechanisms. Plants adopt two strategies (termed I and II) of iron acquisition. Strategy I is adopted by all higher plants except graminaceous plants, which adopt strategy II [ 1 , 2 ]. In strategy I plants, the role of nicotianamine is not fully determined: possible roles include the formation of more stable complexes with ferrous than with ferric ion, which might serve as a sensor of the physiological status of iron within a plant, or which might be involved in the transport of iron [ 3 ]. In strategy II (graminaceous) plants, nicotianamine is the key intermediate (and nicotianamine synthase the key enzyme) in the synthesis of the mugineic family (the only known family in plants) of phytosiderophores. Phytosiderophores are iron chelators whose secretion by the roots is greatly increased in instances of iron deficiency [ 3 ].

The 3D structures of five example NAS from Methanothermobacter thermautotrophicus reveal the monomer to consist of a five-helical bundle N-terminal domain on top of a classic Rossmann fold C-terminal domain. The N-terminal domain is unique to the NAS family, whereas the C-terminal domain is homologous to the class I family of SAM-dependent methyltransferases. An active site is created at the interface of the two domains, at the rim of a large cavity that corresponds to the nucleotide binding site such as is found in other proteins adopting a Rossmann fold [ 3 ].

1. Map-based cloning of chloronerva, a gene involved in iron uptake of higher plants encoding nicotianamine synthase. Proc. Natl. Acad. Sci. U.S.A. 96, 7098-103
2. Cloning of nicotianamine synthase genes, novel genes involved in the biosynthesis of phytosiderophores. Plant Physiol. 119, 471-80
3. Crystallographic snapshots of iterative substrate translocations during nicotianamine synthesis in Archaea. Proc. Natl. Acad. Sci. U.S.A. 106, 16180-4