{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:31:43Z","timestamp":1781109103685,"version":"3.54.1"},"reference-count":18,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,12,19]]},"abstract":"<jats:p>\n                    Conflicting reports have suggested that the silent information\n regulator 2 (SIR2) protein family employs NAD\n                    <jats:sup>+<\/jats:sup>\n                    to\n ADP-ribosylate histones [Tanny, J. C., Dowd, G. J., Huang,\n J., Hilz, H. &amp; Moazed, D. (1999)\n                    <jats:italic>Cell<\/jats:italic>\n                    99, 735\u2013745;\n Frye, R. A. (1999)\n                    <jats:italic>Biochem. Biophys. Res. Commun.<\/jats:italic>\n                    260, 273\u2013279], deacetylate histones [Landry, J., Sutton, A., Tafrov,\n S. T., Heller, R. C., Stebbins, J., Pillus, L. &amp; Sternglanz,\n R. (2000)\n                    <jats:italic>Proc. Natl. Acad. Sci. USA<\/jats:italic>\n                    97, 5807\u20135811;\n Smith, J. S., Brachmann, C. B., Celic, I., Kenna, M. A.,\n Muhammad, S., Starai, V. J., Avalos, J. L.,\n Escalante-Semerena, J. C., Grubmeyer, C., Wolberger, C. &amp; Boeke,\n J. D. (2000)\n                    <jats:italic>Proc. Natl. Acad. Sci. USA<\/jats:italic>\n                    97,\n 6658\u20136663], or both [Imai, S., Armstrong, C. M., Kaeberlein, M.\n &amp; Guarente, L. (2000)\n                    <jats:italic>Nature (London)<\/jats:italic>\n                    403, 795\u2013800].\n Uncovering the true enzymatic function of SIR2 is critical to the basic\n understanding of its cellular function. Therefore, we set out to\n authenticate the reaction products and to determine the intrinsic\n catalytic mechanism. We provide direct evidence that the efficient\n histone\/protein deacetylase reaction is tightly coupled to the\n formation of a previously unidentified acetyl-ADP-ribose product\n (1-\n                    <jats:italic>O<\/jats:italic>\n                    -acetyl-ADP ribose). One molecule of\n NAD\n                    <jats:sup>+<\/jats:sup>\n                    and one molecule of acetyl-lysine are readily\n catalyzed to one molecule of deacetylated lysine, nicotinamide, and\n 1-\n                    <jats:italic>O<\/jats:italic>\n                    -acetyl-ADP-ribose. A unique reaction mechanism\n involving the attack of enzyme-bound acetate or the direct attack of\n acetyl-lysine on an oxocarbenium ADP-ribose intermediate is proposed.\n We suggest that the reported histone\/protein ADP-ribosyltransferase\n activity is a low-efficiency side reaction that can be explained\n through the partial uncoupling of the intrinsic deacetylation and\n acetate transfer to ADP-ribose.\n                  <\/jats:p>","DOI":"10.1073\/pnas.250422697","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"14178-14182","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":488,"title":["Silent information regulator 2 family of NAD- dependent histone\/protein deacetylases generates a unique product, 1-\n                    <i>O-<\/i>\n                    acetyl-ADP-ribose"],"prefix":"10.1073","volume":"97","author":[{"given":"Kirk G.","family":"Tanner","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oregon Health\r Sciences University, Portland, OR 97201-3098; and\r Department of Biochemistry and Cell Biology, State\r University of New York, Stony Brook, NY 11794-5215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Landry","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oregon Health\r Sciences University, Portland, OR 97201-3098; and\r Department of Biochemistry and Cell Biology, State\r University of New York, Stony Brook, NY 11794-5215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Sternglanz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oregon Health\r Sciences University, Portland, OR 97201-3098; and\r Department of Biochemistry and Cell Biology, State\r University of New York, Stony Brook, NY 11794-5215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Denu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Oregon Health\r Sciences University, Portland, OR 97201-3098; and\r Department of Biochemistry and Cell Biology, State\r University of New York, Stony Brook, NY 11794-5215"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,12,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3000"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.11.110195.002511"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90681-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/15458"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.23.2888"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.48.31788"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.110148297"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.12.6658"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81671-2"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/35001622"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.0897"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi001272h"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac960221g"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi970379a"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01187.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3490203"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3420249"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5487.2126"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.250422697","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T09:40:33Z","timestamp":1649842833000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.250422697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12,5]]},"references-count":18,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2000,12,19]]}},"alternative-id":["10.1073\/pnas.250422697"],"URL":"https:\/\/doi.org\/10.1073\/pnas.250422697","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,12,5]]},"assertion":[{"value":"2000-09-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-12-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}