{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T01:05:31Z","timestamp":1782263131106,"version":"3.54.5"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,3,13]]},"abstract":"<jats:p>\n                    The structures of two isoforms of Bcl-2 that differ by two amino\n acids have been determined by NMR spectroscopy. Because wild-type Bcl-2\n behaved poorly in solution, the structures were determined by using\n Bcl-2\/Bcl-x\n                    <jats:sub>L<\/jats:sub>\n                    chimeras in which part of the putative\n unstructured loop of Bcl-2 was replaced with a shortened loop from\n Bcl-x\n                    <jats:sub>L<\/jats:sub>\n                    . These chimeric proteins have a low pI compared with\n the wild-type protein and are soluble. The structures of the two Bcl-2\n isoforms consist of 6 \u03b1-helices with a hydrophobic groove on the\n surface similar to that observed for the homologous protein,\n Bcl-x\n                    <jats:sub>L<\/jats:sub>\n                    . Comparison of the Bcl-2 structures to that of\n Bcl-x\n                    <jats:sub>L<\/jats:sub>\n                    shows that although the overall fold is the same,\n there are differences in the structural topology and electrostatic\n potential of the binding groove. Although the structures of the two\n isoforms of Bcl-2 are virtually identical, differences were observed in\n the ability of the proteins to bind to a 25-residue peptide from the\n proapoptotic Bad protein and a 16-residue peptide from the\n proapoptotic Bak protein. These results suggest that there are\n subtle differences in the hydrophobic binding groove in Bcl-2 that may\n translate into differences in antiapoptotic activity for the\n two isoforms.\n                  <\/jats:p>","DOI":"10.1073\/pnas.041619798","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"3012-3017","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":378,"title":["Solution structure of the antiapoptotic protein bcl-2"],"prefix":"10.1073","volume":"98","author":[{"given":"Andrew M.","family":"Petros","sequence":"first","affiliation":[{"name":"Pharmaceutical Discovery Division, Abbott Laboratories, Abbott\r Park, IL 60064; and IDUN Pharmaceuticals, La Jolla, CA\r 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ales","family":"Medek","sequence":"additional","affiliation":[{"name":"Pharmaceutical Discovery Division, Abbott Laboratories, Abbott\r Park, IL 60064; and IDUN Pharmaceuticals, La Jolla, CA\r 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Nettesheim","sequence":"additional","affiliation":[{"name":"Pharmaceutical Discovery Division, Abbott Laboratories, Abbott\r Park, IL 60064; and IDUN Pharmaceuticals, La Jolla, CA\r 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Pharmaceutical Discovery Division, Abbott Laboratories, Abbott\r Park, IL 60064; and IDUN Pharmaceuticals, La Jolla, CA\r 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Sup","family":"Yoon","sequence":"additional","affiliation":[{"name":"Pharmaceutical Discovery Division, Abbott Laboratories, Abbott\r Park, IL 60064; and IDUN Pharmaceuticals, La Jolla, CA\r 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Swift","sequence":"additional","affiliation":[{"name":"Pharmaceutical Discovery Division, Abbott Laboratories, Abbott\r Park, IL 60064; and IDUN Pharmaceuticals, La Jolla, CA\r 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmund D.","family":"Matayoshi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Discovery Division, Abbott Laboratories, Abbott\r Park, IL 60064; and IDUN Pharmaceuticals, La Jolla, CA\r 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman","family":"Oltersdorf","sequence":"additional","affiliation":[{"name":"Pharmaceutical Discovery Division, Abbott Laboratories, Abbott\r Park, IL 60064; and IDUN Pharmaceuticals, La Jolla, CA\r 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Fesik","sequence":"additional","affiliation":[{"name":"Pharmaceutical Discovery Division, Abbott Laboratories, Abbott\r Park, IL 60064; and IDUN Pharmaceuticals, La Jolla, CA\r 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,2,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1126\/science.6093263","volume":"226","author":"Tsujimoto Y","year":"1984","unstructured":"Y Tsujimoto, L R Finger, J Yunis, P C Nowell, C M Croce Science 226, 1097\u20131099 (1984).","journal-title":"Science"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1073\/pnas.83.14.5214","volume":"83","author":"Tsujimoto Y","year":"1986","unstructured":"Y Tsujimoto, C M Croce Proc Natl Acad Sci USA 83, 5214\u20135218 (1986).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"7439","DOI":"10.1073\/pnas.82.21.7439","volume":"82","author":"Cleary M L","year":"1985","unstructured":"M L Cleary, J Sklar Proc Natl Acad Sci USA 82, 7439\u20137443 (1985).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0092-8674(86)90362-4","volume":"47","author":"Cleary M L","year":"1986","unstructured":"M L Cleary, S D Smith, J Sklar Cell 47, 19\u201328 (1986).","journal-title":"Cell"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S0092-8674(85)80070-2","volume":"41","author":"Bakhsi A","year":"1985","unstructured":"A Bakhsi, J P Jensen, P Goldman, J J Wright, O W McBride, A L Epstein, S J Korsmeyer Cell 41, 899\u2013906 (1985).","journal-title":"Cell"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/j.1460-2075.1988.tb02791.x","volume":"7","author":"Seto M","year":"1988","unstructured":"M Seto, U Jaeger, R D Hockett, W Graninger, S Bennett, P Goldman, S J Korsmeyer EMBO J 7, 123\u2013131 (1988).","journal-title":"EMBO J"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1126\/science.281.5381.1322","volume":"281","author":"Adams J M","year":"1998","unstructured":"J M Adams, S Cory Science 281, 1322\u20131326 (1998).","journal-title":"Science"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/S0962-8924(98)01321-X","volume":"8","author":"Kelekar A","year":"1998","unstructured":"A Kelekar, C B Thompson Trends Cell Biol 8, 324\u2013330 (1998).","journal-title":"Trends Cell Biol"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev.immunol.16.1.395","volume":"16","author":"Chao D T","year":"1998","unstructured":"D T Chao, S J Korsmeyer Annu Rev Immunol 16, 395\u2013419 (1998).","journal-title":"Annu Rev Immunol"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1097\/00001622-199901000-00014","volume":"11","author":"Reed J C","year":"1999","unstructured":"J C Reed Curr Opin Oncol 11, 68\u201375 (1999).","journal-title":"Curr Opin Oncol"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0092-8674(95)90411-5","volume":"80","author":"Yang E","year":"1995","unstructured":"E Yang, J Zha, J Jockel, L H Boise, C B Thompson, S J Korsmeyer Cell 80, 285\u2013291 (1995).","journal-title":"Cell"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1126\/science.7878464","volume":"267","author":"Thompson C B","year":"1995","unstructured":"C B Thompson Science 267, 1456\u20131462 (1995).","journal-title":"Science"},{"key":"e_1_3_4_13_2","first-page":"117","volume":"45","author":"Kusenda J","year":"1998","unstructured":"J Kusenda Neoplasma (Bratisl) 45, 117\u2013122 (1998).","journal-title":"Neoplasma (Bratisl)"},{"key":"e_1_3_4_14_2","first-page":"F151","volume":"1333","author":"Strasser A","year":"1997","unstructured":"A Strasser, D C S Huang, D L Vaux Biochim Biophys Acta 1333, F151\u2013F178 (1997).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1089\/cbr.1998.13.225","volume":"13","author":"Berghella A M","year":"1998","unstructured":"A M Berghella, P Pellegrini, I Contasta, T Del Beato, D Adorno Cancer Biother Radiopharm 13, 225\u2013236 (1998).","journal-title":"Cancer Biother Radiopharm"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/35037747","volume":"407","author":"Nicholson D W","year":"2000","unstructured":"D W Nicholson Nature (London) 407, 810\u2013816 (2000).","journal-title":"Nature (London)"},{"key":"e_1_3_4_17_2","first-page":"2134","volume":"58","author":"Piche A","year":"1998","unstructured":"A Piche, J Grim, C Rancourt, J Gomez-Navarro, J C Reed, D T Curiel Cancer Res 58, 2134\u20132140 (1998).","journal-title":"Cancer Res"},{"key":"e_1_3_4_18_2","first-page":"1498","volume":"60","author":"Wang J L","year":"2000","unstructured":"J L Wang, Z J Zhang, S Choksi, S Shan, Z Lu, C M Croce, E S Alnemri, R Korngold, Z Huang Cancer Res 60, 1498\u20131502 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"7124","DOI":"10.1073\/pnas.97.13.7124","volume":"97","author":"Wang J L","year":"2000","unstructured":"J L Wang, D Liu, Z J Zhang, S Shan, X Han, S M Srinvasula, C M Croce, E S Alnemri, Z Huang Proc Natl Acad Sci USA 97, 7124\u20137129 (2000).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/381335a0","volume":"381","author":"Muchmore S W","year":"1996","unstructured":"S W Muchmore, M Sattler, H Liang, R P Meadows, J E Harlan, H S Yoon, D Nettesheim, B S Chang, C B Thompson, S L Wong, et al. Nature (London) 381, 335\u2013341 (1996).","journal-title":"Nature (London)"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1126\/science.275.5302.983","volume":"275","author":"Sattler M","year":"1997","unstructured":"M Sattler, H Liang, D Nettesheim, R P Meadows, J E Harlan, M Eberstadt, H S Yoon, S B Shuker, B S Chang, A J Minn, et al. Science 275, 983\u2013986 (1997).","journal-title":"Science"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","unstructured":"Petros A. M. Nettesheim D. G. Wang Y. Olejniczak E. T. Meadows R. P. Mack J. Swift K. Matayoshi E. D. Zhang H. Thompson C. B. & Fesik S. W. (2000) Protein Sci. 9 in press.","DOI":"10.1017\/S096183680000331X"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0092-8674(93)80065-M","volume":"75","author":"Veis D J","year":"1993","unstructured":"D J Veis, C M Sorenson, J R Shutter, S J Korsmeyer Cell 75, 229\u2013240 (1993).","journal-title":"Cell"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1073\/pnas.91.9.3700","volume":"91","author":"Nakayama K","year":"1994","unstructured":"K Nakayama, I Negishi, K Kuida, H Sawa, D Y Loh Proc Natl Acad Sci USA 91, 3700\u20133704 (1994).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_25_2","first-page":"354","volume":"55","author":"Kamada S","year":"1995","unstructured":"S Kamada, A Shimono, Y Shinto, T Tsujimura, T Takahashi, T Noda, Y Kitamura, H Kondoh, Y Tsujimoto Cancer Res 55, 354\u2013359 (1995).","journal-title":"Cancer Res"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1126\/science.7878471","volume":"267","author":"Motoyama N","year":"1995","unstructured":"N Motoyama, F Wang, K A Roth, H Sawa, K Nakayama, I Negishi, S Senju, Q Zhang, S Fujii, D Y Loh Science 267, 1506\u20131510 (1995).","journal-title":"Science"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/0092-8674(93)90508-N","volume":"74","author":"Boise L H","year":"1993","unstructured":"L H Boise, M Gonzalez-Garcia, C E Postema, L Ding, T Lindsten, L A Turka, X Mao, G Nunez, C B Thompson Cell 74, 597\u2013608 (1993).","journal-title":"Cell"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1182\/blood.V81.11.3091.3091","volume":"81","author":"Campos L","year":"1993","unstructured":"L Campos, J P Rouault, O Sabido, P Oriol, N Roubi, C Vasselon, E Archimbund, J P Magaud, D Guyotat Blood 81, 3091\u20133096 (1993).","journal-title":"Blood"},{"key":"e_1_3_4_29_2","first-page":"230","volume":"3","author":"Olopade O I","year":"1997","unstructured":"O I Olopade, M O Adeyanju, A R Safa, F Hagos, R Mick, C B Thompson, W M Recant Cancer J Sci Am 3, 230\u2013237 (1997).","journal-title":"Cancer J Sci Am"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"30866","DOI":"10.1074\/jbc.272.49.30866","volume":"272","author":"Ottilie S","year":"1997","unstructured":"S Ottilie, J L Diaz, W Horne, J Chang, Y Wang, G Wilson, S Chang, S Weeks, L C Fritz, T Oltersdorf J Biol Chem 272, 30866\u201330872 (1997).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"11655","DOI":"10.1021\/ja00105a005","volume":"116","author":"Yamazaki T","year":"1994","unstructured":"T Yamazaki, W Lee, C H Arrowsmith, D R Muhandiram, L E Kay J Am Chem Soc 116, 11655\u201311666 (1994).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0076-6879(94)39013-4","volume":"239","author":"Clore G M","year":"1994","unstructured":"G M Clore, A M Gronenborn Methods Enzymol 239, 349\u2013363 (1994).","journal-title":"Methods Enzymol"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"7510","DOI":"10.1021\/bi00445a003","volume":"28","author":"Neri D","year":"1989","unstructured":"D Neri, T Szyperski, G Otting, H Senn, K W\u00fcthrich Biochemistry 28, 7510\u20137516 (1989).","journal-title":"Biochemistry"},{"key":"e_1_3_4_34_2","first-page":"588","volume":"78","author":"Fesik S W","year":"1988","unstructured":"S W Fesik, E R P Zuiderweg J Magn Reson 78, 588\u2013593 (1988).","journal-title":"J Magn Reson"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"6150","DOI":"10.1021\/bi00441a004","volume":"29","author":"Marion D","year":"1989","unstructured":"D Marion, P C Driscoll, L E Kay, P T Wingfield, A Bax, A M Gronenborn, G M Clore Biochemistry 29, 6150\u20136156 (1989).","journal-title":"Biochemistry"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"R205","DOI":"10.1016\/S0969-2126(99)80167-1","volume":"7","author":"Tjandra N","year":"1999","unstructured":"N Tjandra Structure (London) 7, R205\u2013R211 (1999).","journal-title":"Structure (London)"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/4176","volume":"5","author":"Hansen M R","year":"1998","unstructured":"M R Hansen, L Mueller, A Pardi Nat Struct Biol 5, 1065\u20131074 (1998).","journal-title":"Nat Struct Biol"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"10571","DOI":"10.1021\/ja982592f","volume":"120","author":"Clore G M","year":"1998","unstructured":"G M Clore, M R Starich, A M Gronenborn J Am Chem Soc 120, 10571\u201310572 (1998).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_39_2","volume-title":"x-plor Version 3.1 manual","author":"Brunger A T","year":"1992","unstructured":"A T Brunger x-plor Version 3.1 manual (Yale Univ. Press, London, 1992)."},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1023\/A:1008392405740","volume":"13","author":"Cornilescu G","year":"1999","unstructured":"G Cornilescu, F Delaglio, A Bax J Biomol NMR 13, 289\u2013302 (1999).","journal-title":"J Biomol NMR"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","volume":"26","author":"Laskowski R A","year":"1993","unstructured":"R A Laskowski, M W MacArthur, D S Moss, J M Thornton J Appl Crystallogr 26, 283\u2013291 (1993).","journal-title":"J Appl Crystallogr"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0076-6879(81)74003-5","volume":"74","author":"Dandliker W B","year":"1981","unstructured":"W B Dandliker, M L Hsu, J Levin, B R Rao Methods Enzymol 74, 3\u201328 (1981).","journal-title":"Methods Enzymol"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1006\/prep.1998.0996","volume":"15","author":"Anderson M","year":"1999","unstructured":"M Anderson, D Blowers, N Hewitt, P Hedge, A Breeze, I Hampton, I Taylor Protein Expression Purif 15, 162\u2013170 (1999).","journal-title":"Protein Expression Purif"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/369321a0","volume":"369","author":"Yin X M","year":"1994","unstructured":"X M Yin, Z N Oltvai, S J Korsmeyer Nature (London) 369, 321\u2013323 (1994).","journal-title":"Nature (London)"},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/prot.340110407","volume":"11","author":"Nichols A J","year":"1991","unstructured":"A J Nichols, K A Sharp, B Honig Proteins Struct Funct Genet 11, 281\u2013296 (1991).","journal-title":"Proteins Struct Funct Genet"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S0092-8674(00)00167-7","volume":"103","author":"Suzuki M","year":"2000","unstructured":"M Suzuki, R J Youle, N Tjandra Cell 103, 645\u2013654 (2000).","journal-title":"Cell"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0263-7855(87)80010-3","volume":"5","author":"Carson M","year":"1987","unstructured":"M Carson J Mol Graphics 5, 103\u2013106 (1987).","journal-title":"J Mol Graphics"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.041619798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T01:35:07Z","timestamp":1654565707000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.041619798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,2,27]]},"references-count":47,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2001,3,13]]}},"alternative-id":["10.1073\/pnas.041619798"],"URL":"https:\/\/doi.org\/10.1073\/pnas.041619798","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,2,27]]},"assertion":[{"value":"2000-11-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-12-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}