Lysine 2,3-aminomutase
| Lysine 2,3-aminomutase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 5.4.3.2 | ||||||||
| CAS no. | 9075-20-1 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
Lysine 2,3-aminomutase (KAM or LAM) (EC 5.4.3.2) is a radical SAM enzyme that facilitates the conversion of the amino acid lysine to beta-lysine.[1][2] [3][4] 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:
Structure[edit]
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.
Cofactors[edit]
Four key cofactors are required for the reaction catalyzed by the lysine 2,3-aminomutase enzyme. They are:
- S-Adenosyl methionine (SAM): Helps generate the radical intermediate by borrowing an electron.[5]
- 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.
Reaction Mechanism[edit]
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:
References[edit]
- ^ Frey PA (May 1993). "Lysine 2,3-aminomutase: is adenosylmethionine a poor man's adenosylcobalamin?". FASEB Journal. 7 (8): 662–70. doi:10.1096/fasebj.7.8.8500691. PMID 8500691. S2CID 33374466.
- ^ Lepore BW, Ruzicka FJ, Frey PA, Ringe D (September 2005). "The x-ray crystal structure of lysine-2,3-aminomutase from Clostridium subterminale". Proceedings of the National Academy of Sciences of the United States of America. 102 (39): 13819–24. Bibcode:2005PNAS..10213819L. doi:10.1073/pnas.0505726102. PMC 1236562. PMID 16166264.
- ^ Aberhart DJ, Gould SJ, Lin HJ, Thiruvengadam TK, Weiller BH (1981). "Stereochemistry of lysine 2,3-aminomutase". J. Am. Chem. Soc. 103 (22): 6750–6752. doi:10.1021/ja00412a040.
- ^ Zappia V, Barker HA (June 1970). "Studies on lysine-2,3-aminomutase. Subunit structure and sulfhydryl groups". Biochimica et Biophysica Acta. 207 (3): 505–13. doi:10.1016/s0005-2795(70)80013-7. PMID 5452674.
- ^ Bhandari DM, Fedoseyenko D, Begley TP (2018). "Mechanistic Studies on the Radical SAM Enzyme Tryptophan Lyase (NosL)". Radical SAM Enzymes. Methods in Enzymology. Vol. 606. pp. 155–178. doi:10.1016/bs.mie.2018.06.008. ISBN 9780128127940. PMID 30097091.
External links[edit]
- Lysine+2,3-aminomutase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
