{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:27:06Z","timestamp":1790774826182,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T00:00:00Z","timestamp":1555286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>An increased level of homocysteine, a reactive thiol amino acid, is associated with several complex disorders and is an independent risk factor for cardiovascular disease. A majority (&gt;80%) of circulating homocysteine is protein bound. Homocysteine exclusively binds to protein cysteine residues via thiol disulfide exchange reaction, the mechanism of which has been reported. In contrast, homocysteine thiolactone, the cyclic thioester of homocysteine, is believed to exclusively bind to the primary amine group of lysine residue leading to N\u2010homocysteinylation of proteins and hence studies on binding of homocysteine thiolactone to proteins thus far have only focused on N\u2010homocysteinylation. Although it is known that homocysteine thiolactone can hydrolyze to homocysteine at physiological pH, surprisingly the extent of S\u2010homocysteinylation during the exposure of homocysteine thiolactone with proteins has never been looked into. In this study, we clearly show that the hydrolysis of homocysteine thiolactone is pH dependent, and at physiological pH, 1 mM homocysteine thiolactone is hydrolysed to ~0.71\u2009mM homocysteine within 24\u2009h. Using albumin, we also show that incubation of HTL with albumin leads to a greater proportion of S\u2010homocysteinylation (0.41\u2009mol\/mol of albumin) than N\u2010homocysteinylation (0.14\u2009mol\/mol of albumin). S\u2010homocysteinylation at Cys<jats:sup>34<\/jats:sup> of HSA on treatment with homocysteine thiolactone was confirmed using LC\u2010MS. Further, contrary to earlier reports, our results indicate that there is no cross talk between the cysteine attached to Cys<jats:sup>34<\/jats:sup> of albumin and homocysteine attached to lysine residues.<\/jats:p>","DOI":"10.1002\/prot.25681","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T15:44:29Z","timestamp":1552578269000},"page":"625-634","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Hydrolysis of homocysteine thiolactone results in the formation of Protein\u2010Cys\u2010S\u2010S\u2010homocysteinylation"],"prefix":"10.1002","volume":"87","author":[{"given":"Yumnam","family":"Silla","sequence":"first","affiliation":[{"name":"Department of Genomics and Molecular Medicine CSIR\u2010Institute of Genomics and Integrative Biology  New Delhi Delhi India"},{"name":"Academy of Scientific &amp; Innovative Research (AcSIR)  New Delhi Delhi 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