Lysine 2,3-aminomutase
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[edit] General Reaction
Lysine 2,3-aminomutase (KAM or LAM) (EC |5.4.3.2) is an enzyme which 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.[1] The generalized reaction is shown below:
[edit] 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.[2] KAM was first purified and characterized in Clostridium subterminale for studies of Lysine metabolism.
[edit] Cofactors
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.
[edit] 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 stablizied 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:
[edit] References
[1] Frey, P.A. "Lysine 2,3-aminomutase: is adenosylmethionine a poor man's adenosylcobalamin. FASEB Jour.; 1993; Vol. 7, 662-670.
[2] 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.
