Lysine 2,3-aminomutase

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

radical SAM Radical SAM enzymes belong to a superfamily of enzymes that use an iron-sulfur cluster (4Fe-4S) to reductively cleave S-Adenosyl methionine, ''S''-adenosyl-L-methionine (SAM) to generate a radical (chemistry), radical, usually a 5′-deoxyadenosyl ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that facilitates the conversion of the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

to beta-lysine. It accomplishes this interconversion using three cofactors 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 thro ...

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

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 of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring th ...
to 2.1 Angstrom resolution and was seen to crystallize as a homotetramer.^{/sup> KAM was first purified and characterized in ''Clostridium

''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tracts of animals, including humans. This genus includes several significant human pathogens, including the causative ...
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 thro ...
(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-dependen ...
(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 enzymes belong to a superfamily of enzymes that use an iron-sulfur cluster (4Fe-4S) to reductively cleave S-Adenosyl methionine, ''S''-adenosyl-L-methionine (SAM) to generate a radical (chemistry), radical, usually a 5′-deoxyadenosyl ...
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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