Lysine 2,3-aminomutase

Lysine 2,3-aminomutase (KAM or LAM) () is a

radical SAM Radical SAM is a designation for a superfamily of enzymes that use a +_cluster.html" ;"title="Fe-4Ssup>+ cluster">Fe-4Ssup>+ cluster to reductively cleave ''S''-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′- deoxyadenosyl rad ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that facilitates the conversion of the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

to beta-lysine. It accomplishes this interconversion using three

cofactors Cofactor may also refer to: * Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed * A domain parameter in elliptic curve cryptography, defined as the ratio between the order ...

and a 5'- deoxyadenosyl radical formed in a

S-Adenosyl methionine ''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...

(SAM) activated radical reaction pathway.^{/sup> 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

X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
to 2.1 Angstrom resolution and was seen to crystallize as a homotetramer.^{/sup> 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

''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...
(SAM): Helps generate the radical intermediate by borrowing an electron.
* Pyridoxal phosphate

Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent a ...
(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
Radical SAM is a designation for a superfamily of enzymes that use a +_cluster.html" ;"title="Fe-4Ssup>+ cluster">Fe-4Ssup>+ cluster to reductively cleave ''S''-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′- deoxyadenosyl rad ...
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

External links

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