Lysine 2,3-aminomutase

Shown on the right is the three-dimensional structure of the Lysine 2,3-aminomutase protein. The structure was determined by X-ray crystallography to 2.1 Angstrom resolution and was seen to crystallize as a homotetramer.[2] KAM was first purified and characterized in Clostridium subterminale for studies of Lysine metabolism. == Cofactors ==

Four key cofactors are required for the reaction catalyzed by the lysine 2,3-aminomutase enzyme. They are: • S-Adenosyl methionine (SAM): Helps generate the radical intermediate by borrowing an electron. • Pyridoxal phosphate (PLP): Responsible for binding of the amino acid during reaction. The pi-system of this molecule facilitates radical delocalization during formation of an aziridinyl radical. The structure is given below: • Zinc metal: Required for coordination between the dimers in the protein. • Iron-sulfur cluster: A 4 iron-4 sulfur cluster is required for formation of a 5'-deoxyadenosyl radical. This radical then acts as the "stable" radical carrier in the reaction mechanism which transfers the radical to the amino acid. == Reaction Mechanism ==

The generalized reaction takes place in 5 steps: • Radical Formation: A "stable" radical is formed through a radical SAM mechanism in which a S-adenosyl methionine forms a 5'-deoxyadenosyl radical. • Enzyme Binding: Lysine 2,3-aminomutase binds to pyridoxal phosphate (PLP). • Amino Acid Binding: The amino acid (Lysine or Beta-Lysine depending on forward or reverse reactions) binds to pyridoxal phosphate. • Radical Transfer: The 5'-deoxyadenosyl radical is transferred to the amino acid and an aziridinyl radical is formed. In this configuration, the radical is stabilized by the pi-system of pyridoxal phosphate. • Amino Acid Conversion: In the final step, the new amino acid is formed and the radical is returned to its more stable state on the 5'-deoxyadenosyl. The reaction mechanism described above is shown below: == References ==