Lysine 2,3-aminomutase


Lysine 2,3-aminomutase is a radical SAM enzyme that facilitates the conversion of the amino acid lysine to beta-lysine.
It accomplishes this interconversion using three cofactors and a 5'-deoxyadenosyl radical formed in a S-Adenosyl methionine activated radical reaction pathway. The generalized reaction is shown below:

Structure

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. 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:
The generalized reaction takes place in 5 steps:
  1. Radical Formation: A "stable" radical is formed through a radical SAM mechanism in which a S-adenosyl methionine forms a 5'-deoxyadenosyl radical.
  2. Enzyme Binding: Lysine 2,3-aminomutase binds to pyridoxal phosphate.
  3. Amino Acid Binding: The amino acid binds to pyridoxal phosphate.
  4. 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.
  5. 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: