Homocysteine thiolactone

Homocysteine thiolactone (HTL) is an organosulfur compound with the formula H₂NCHC(O)SCH₂CH₂. It is the thiolactone (intramolecular thioester) of homocysteine. It is produced by methionyl-tRNA synthetase in an error-editing reaction that prevents translational incorporation of homocysteine into proteins.

Homocysteine thiolactone

Names
IUPAC name (3S)-3-aminothiolan-2-one
Identifiers
CAS Number	2338-04-7
3D model (JSmol)	Interactive image
Beilstein Reference	80591
ChEBI	CHEBI:60315
ChEMBL	ChEMBL4078313
ChemSpider	118559
PubChem CID	134505
InChI InChI=1S/C4H7NOS/c5-3-1-2-7-4(3)6/h3H,1-2,5H2/t3-/m0/s1 Key: KIWQWJKWBHZMDT-VKHMYHEASA-N
SMILES C1CSC(=O)[C@H]1N
Properties
Chemical formula	C4H7NOS
Molar mass	117.17 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

HTL can damage proteins through "homocysteinylation" of protein lysine residues.^[1] HTL has been reported to form isopeptide bonds with lysine residues in substrate proteins, a post-translational modification known as N-homocysteinylation (N-Hcy). This causes protein damage via a thiyl radical mechanism.^[2] The drugs citiolone and erdosteine are modified versions of homocysteine thiolactone.

When N-Hcy binds α-syn, it exacerbates α-syn aggregation, neurotoxicity, and dopaminergic neuronal degeneration. It also damages the protein DJ-1, contributing to Parkinson's disease.^[3]