{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:24:56Z","timestamp":1781105096329,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,4,30]]},"abstract":"<jats:p>The marine natural product didemnin B, currently in clinical trials as an antitumor agent, has several potent biological activities apparently mediated by distinct mechanisms. Our initial investigation of didemnin B resulted in the discovery of its GTP-dependent binding of the translation elongation factor EF1 alpha. This finding is consistent with the protein synthesis inhibitory activity of didemnin B observed at intermediate concentrations. To begin to dissect the mechanisms involved in the cytostatic and immunosuppressive activities of didemnin B, observed at low concentrations, additional didemnin-binding proteins were sought. Here we report the purification of a 36-kDa glycosylated didemnin-binding protein from bovine brain lysate. Cloning of the human cDNA encoding this protein revealed a strong sequence similarity with palmitoyl protein thioesterase (PPT), an enzyme that removes palmitate from H-Ras and the G alpha s subunits of heterotrimeric GTP-binding proteins in vitro. Mutations in PPT have recently been shown to be responsible for infantile neuronal ceroid lipofuscinosis, which is a severe brain disorder characterized by progressive loss of brain function and early death.<\/jats:p>","DOI":"10.1073\/pnas.93.9.4316","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:07Z","timestamp":1027679707000},"page":"4316-4319","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":43,"title":["Didemnin binds to the protein palmitoyl thioesterase responsible for infantile neuronal ceroid lipofuscinosis."],"prefix":"10.1073","volume":"93","author":[{"given":"C M","family":"Crews","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cambridge MA, USA. craig.crews@yale.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W S","family":"Lane","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cambridge MA, USA. craig.crews@yale.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S L","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Cambridge MA, USA. craig.crews@yale.edu"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,4,30]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.9.4316","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T15:02:44Z","timestamp":1649862164000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.9.4316"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,4,30]]},"references-count":0,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1996,4,30]]}},"alternative-id":["10.1073\/pnas.93.9.4316"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.9.4316","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,4,30]]},"assertion":[{"value":"1996-04-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}