Homocysteine-thiolactone
Substrate of many non alpha/beta hydrolases: PON paraoxonase/arylesterase 6-blade_b-propeller_TolB-lik, Bleomycin hydrolase (BLMH IPR038765 Papain-like_cys IPR004134 Peptidase_C) and also alpha/beta hydrolases Valacyclovir-hydrolase Carboxylesterases. Homocysteine thiolactone, slowly and irreversibly inhibited the activity of human AChE but significantly enhanced the activity of human BuChE. Some protein oligomers are disulfide cross-linked, native-like, and obtained as a result of the covalent modification of the proteins by the toxic metabolite, homocysteine thiolactone accumulated under hyperhomocysteinemia. Circulating homocysteine is protein bound. Homocysteine exclusively binds to protein cysteine residues via thiol disulfide exchange reaction. In contrast, homocysteine thiolactone, the cyclic thioester of homocysteine exclusively binds to the primary amine group of lysine residue leading to N-homocysteinylation of proteins
General
Type : Natural, Sulfur Compound, Not AlphaBeta Hydrolase target, Thiophen
Chemical_Nomenclature : (3S)-3-aminothiolan-2-one
Canonical SMILES : C1CSC(=O)C1N
InChI : InChI=1S\/C4H7NOS\/c5-3-1-2-7-4(3)6\/h3H,1-2,5H2\/t3-\/m0\/s1
InChIKey : KIWQWJKWBHZMDT-VKHMYHEASA-N
Other name(s) : Homocysteine thiolactone || (S)-3-Aminodihydrothiophen-2(3H)-one || L-Homocysteine thiolactone || SCHEMBL2167191 || CHEMBL4078313 || BDBM86198 || CHEBI:60315 || DL-Homocysteine thiolactone || (3R)-3-aminothiolan-2-one || D-Homocysteinethiolactone
MW : 117.17
Formula : C4H7NOS
CAS_number : 2338-04-7, 10593-85-8, 14007-10-4, 130548-06-0
PubChem : 134505, 107712, 7057932
UniChem : KIWQWJKWBHZMDT-VKHMYHEASA-N
Wikipedia : Homocysteine_thiolactone
Target
Structures : No structure
Families : Valacyclovir-hydrolase, Carb_B_Chordata, BCHE
References (10)
| Title : Discovery of a novel homocysteine thiolactone hydrolase and the catalytic activity of its natural variants - Hou_2024_Protein.Sci_33_e5098 |
| Author(s) : Hou S , Liu H , Hu Y , Zhang J , Deng X , Li Z , Zhang Y , Li X , Li Y , Ma L , Yao J , Chen X |
| Ref : Protein Science , 33 :e5098 , 2024 |
| Abstract : |
| PubMedSearch : Hou_2024_Protein.Sci_33_e5098 |
| PubMedID: 38980003 |
| Title : Deletion of the Homocysteine Thiolactone Detoxifying Enzyme Bleomycin Hydrolase, in Mice, Causes Memory and Neurological Deficits and Worsens Alzheimer's Disease-Related Behavioral and Biochemical Traits in the 5xFAD Model of Alzheimer's Disease - Witucki_2023_J.Alzheimers.Dis_95_1735 |
| Author(s) : Witucki L , Borowczyk K , Suszynska-Zajczyk J , Warzych E , Pawlak P , Jakubowski H |
| Ref : J Alzheimers Dis , 95 :1735 , 2023 |
| Abstract : |
| PubMedSearch : Witucki_2023_J.Alzheimers.Dis_95_1735 |
| PubMedID: 37718819 |
| Title : Functionally active cross-linked protein oligomers formed by homocysteine thiolactone - Kumari_2023_Sci.Rep_13_5620 |
| Author(s) : Kumari K , Sharma GS , Gupta A , Singh KS , Singh LR |
| Ref : Sci Rep , 13 :5620 , 2023 |
| Abstract : |
| PubMedSearch : Kumari_2023_Sci.Rep_13_5620 |
| PubMedID: 37024663 |
| Title : Hydrolysis of homocysteine thiolactone results in the formation of Protein-Cys-S-S-homocysteinylation - Silla_2019_Proteins_87_625 |
| Author(s) : Silla Y , Varshney S , Ray A , Basak T , Zinellu A , Sabareesh V , Carru C , Sengupta S |
| Ref : Proteins , 87 :625 , 2019 |
| Abstract : |
| PubMedSearch : Silla_2019_Proteins_87_625 |
| PubMedID: 30869815 |
| Title : Human valacyclovir hydrolase\/biphenyl hydrolase-like protein is a highly efficient homocysteine thiolactonase - Marsillach_2014_PLoS.One_9_e110054 |
| Author(s) : Marsillach J , Suzuki SM , Richter RJ , McDonald MG , Rademacher PM , Maccoss MJ , Hsieh EJ , Rettie AE , Furlong CE |
| Ref : PLoS ONE , 9 :e110054 , 2014 |
| Abstract : |
| PubMedSearch : Marsillach_2014_PLoS.One_9_e110054 |
| PubMedID: 25333274 |
| Gene_locus related to this paper: human-BPHL |
| Title : Paraoxonase 1 and homocysteine metabolism - Perla-Kajan_2012_Amino.Acids_43_1405 |
| Author(s) : Perla-Kajan J , Jakubowski H |
| Ref : Amino Acids , 43 :1405 , 2012 |
| Abstract : |
| PubMedSearch : Perla-Kajan_2012_Amino.Acids_43_1405 |
| PubMedID: 22643843 |
| Title : Metabolism and neurotoxicity of homocysteine thiolactone in mice: evidence for a protective role of paraoxonase 1 - Borowczyk_2012_J.Alzheimers.Dis_30_225 |
| Author(s) : Borowczyk K , Shih DM , Jakubowski H |
| Ref : J Alzheimers Dis , 30 :225 , 2012 |
| Abstract : |
| PubMedSearch : Borowczyk_2012_J.Alzheimers.Dis_30_225 |
| PubMedID: 22406444 |
| Title : The role of paraoxonase 1 in the detoxification of homocysteine thiolactone - Jakubowski_2010_Adv.Exp.Med.Biol_660_113 |
| Author(s) : Jakubowski H |
| Ref : Advances in Experimental Medicine & Biology , 660 :113 , 2010 |
| Abstract : |
| PubMedSearch : Jakubowski_2010_Adv.Exp.Med.Biol_660_113 |
| PubMedID: 20221875 |
| Title : Homocysteine thiolactone and human cholinesterases - Darvesh_2007_Cell.Mol.Neurobiol_27_33 |
| Author(s) : Darvesh S , Walsh R , Martin E |
| Ref : Cellular Molecular Neurobiology , 27 :33 , 2007 |
| Abstract : |
| PubMedSearch : Darvesh_2007_Cell.Mol.Neurobiol_27_33 |
| PubMedID: 16955366 |
| Title : A versatile equation to describe reversible enzyme inhibition and activation kinetics: modeling beta-galactosidase and butyrylcholinesterase - Walsh_2007_Biochim.Biophys.Acta_1770_733 |
| Author(s) : Walsh R , Martin E , Darvesh S |
| Ref : Biochimica & Biophysica Acta , 1770 :733 , 2007 |
| Abstract : |
| PubMedSearch : Walsh_2007_Biochim.Biophys.Acta_1770_733 |
| PubMedID: 17307293 |