|PDB structures||RCSB PDB PDBe PDBsum|
Lysine 2,3-aminomutase (KAM or LAM) (EC 184.108.40.206) 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 (SAM) activated radical reaction pathway. The generalized reaction is shown below:
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.
Three key cofactors are required for the reaction catalyzed by the lysine 2,3-aminomutase enzyme. They are:
- 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.
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:
- Frey, P.A. "Lysine 2,3-aminomutase: is adenosylmethionine a poor man's adenosylcobalamin. FASEB Jour.; 1993; Vol. 7, 662-670.
- Lepore, B.; Ruzicka, F.J.; Frey, P.A.; Ringe, D. "The x-ray crystal structure of lysine-2,3-aminomutase from Clostridium subterminale. PNAS; 2005; 102, 13819-13824.
- Aberhart, D.J., Lim, H.-J. and Weiller, B.H. (1981). "Stereochemistry of lysine 2,3-aminomutase". J. Am. Chem. Soc. 103: 6750–6752. doi:10.1021/ja00412a040.
- Zappia, V. and Barker, H.A. (1970). "Studies on lysine-2,3-aminomutase. Subunit structure and sulfhydryl groups". Biochim. Biophys. Acta 207: 505–513. doi:10.1016/s0005-2795(70)80013-7. PMID 5452674.