Lipoyl synthase

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Lipoyl synthase
Identifiers
EC no.2.8.1.8
CAS no.189398-80-9
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

Lipoyl synthase is an enzyme that belongs to the radical SAM (S-adenosylmethionine) family. Within the radical SAM superfamily, lipoyl synthase is in a sub-family of enzymes that catalyze sulfur insertion reactions. Enzymes in this family contain two 4Fe-4S clusters, from which they obtain the sulfur groups that will be transferred onto the corresponding substrates.[1] This particular enzyme participates in lipoic acid metabolism, so it transfers two sulfurs from its 4Fe-4S cluster onto the protein N6-(octanoyl)lysine through radical generation. This enzyme is usually localized to the mitochondria. Two organisms that have been extensively studied with regards to this enzyme are Escherichia coli and Mycobacterium tuberculosis. It is also found in other organisms, such as yeast and plants.

Nomenclature[]

The systematic name of this enzyme class is protein N6-(octanoyl)lysine:sulfur sulfurtransferase. Other names in common use include:

  • LS,
  • LipA,
  • lipoate synthase, and
  • protein 6-N-(octanoyl)lysine:sulfur sulfurtransferase.

Mechanism of lipoyl synthase[]

Lipoyl synthase uses two sulfurs from one of its two [4Fe-4S] clusters and attaches them to the 6th and 8th carbon of the protein N6-(octanoyl)lysine substrate, to convert it into protein N6-(lipoyl)lysine. The other [4Fe-4S] cluster is coordinated by the radical SAM motif of the enzyme (CxxxCxxC) and participates in radical SAM characteristic chemistry to activate the substrate for subsequent sulfur insertion.[2] Below is the overall reaction for this enzyme:

All in all, the 3 substrates of this enzyme are protein N6-(octanoyl)lysine, sulfur, and S-adenosyl-L-methionine, whereas its 3 products are protein N6-(lipoyl)lysine, L-methionine, and 5'-deoxyadenosine.

Importance of lipoyl synthase[]

This enzyme participates in lipoic acid metabolism, where it performs the final step in lipoic acid biosynthesis. Lipoic acid is a cofactor that has different functions within different organisms.[3] The lipoic acid generation in yeast cells increases the number of divisions in the cells as well as protects yeast cells from hydrogen peroxide.[4] Lipoic acid is an important co-factor in many enzyme systems, and one of them is the pyruvate dehydrogenase complex.[5] Studies that repressed the function of lipoyl synthase in Arabidopsis thaliana seeds showed that this did not have adverse effects on seed growth and weight, but shortened the generation time as well as the flowering time of the plants. Repression resulted in earlier flowering times, and decreased the generation times between seeds by almost 10%.[6]

Possible side effects[]

Overexpression of this enzyme in sunflower plants has been found to eventually sequester the amount of SAM present in transgenic Arabidopsis plants. SAM is a molecule that is required in other enzymatic complexes found in this plant as well, as well as the overall structure of the plant, so this sequestration may cause a reduction in the fatty acid biosynthesis in the Arabidopsis seeds.[7]

References[]

  1. ^ McLaughlin MI, Lanz ND, Goldman PJ, Lee KH, Booker SJ, Drennan CL (August 2016). "Crystallographic snapshots of sulfur insertion by lipoyl synthase". Proceedings of the National Academy of Sciences of the United States of America. 113 (34): 9446–50. doi:10.1073/pnas.1602486113. PMC 5003258. PMID 27506792.
  2. ^ Jarrett JT (February 2015). "The biosynthesis of thiol- and thioether-containing cofactors and secondary metabolites catalyzed by radical S-adenosylmethionine enzymes". The Journal of Biological Chemistry. 290 (7): 3972–9. doi:10.1074/jbc.R114.599308. PMC 4326807. PMID 25477512.
  3. ^ "InterPro". www.ebi.ac.uk. Retrieved 2020-04-20.
  4. ^ Della Croce C, Bronzetti G, Cini M, Caltavuturo L, Poi G (2003-10-01). "Protective effect of lipoic acid against hydrogen peroxide in yeast cells". Toxicology in Vitro. Twelfth International Workshop on In vitro Toxicology. 17 (5–6): 753–9. doi:10.1016/j.tiv.2003.06.001. PMID 14599473.
  5. ^ "Lipoic Acid". Linus Pauling Institute. 2014-04-28. Retrieved 2020-04-20.
  6. ^ Zou J, Qi Q, Katavic V, Marillia EF, Taylor DC (December 1999). "Effects of antisense repression of an Arabidopsis thaliana pyruvate dehydrogenase kinase cDNA on plant development". Plant Molecular Biology. 41 (6): 837–49. doi:10.1023/a:1006393726018. OCLC 672002645. PMID 10737148. S2CID 8099883.
  7. ^ Martins-Noguerol R, Moreno-Pérez AJ, Sebastien A, Troncoso-Ponce MA, Garcés R, Thomasset B, et al. (February 2020). "Impact of sunflower (Helianthus annuus L.) plastidial lipoyl synthases genes expression in glycerolipids composition of transgenic Arabidopsis plants". Scientific Reports. 10 (1): 3749. Bibcode:2020NatSR..10.3749M. doi:10.1038/s41598-020-60686-z. PMC 7048873. PMID 32111914.

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