{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T21:08:58Z","timestamp":1774559338825,"version":"3.50.1"},"reference-count":78,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T00:00:00Z","timestamp":1230681600000},"content-version":"vor","delay-in-days":5235,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[1994,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The refined structure of dimeric diphtheria toxin (DT) at 2.0 \u00c5 resolution, based on 37,727 unique reflections (<jats:italic>F<\/jats:italic> &gt; 1\u03c3(<jats:italic>F<\/jats:italic>)), yields a final <jats:italic>R<\/jats:italic> factor of 19.5% with a model obeying standard geometry. The refined model consists of 523 amino acid residues, 1 molecule of the bound dinucleotide inhibitor adenylyl 3\u2032\u20105\u2032 uridine 3\u2032 monophosphate (ApUp), and 405 well\u2010ordered water molecules. The 2.0\u2010\u00c5 refined model reveals that the binding motif for ApUp includes residues in the catalytic and receptor\u2010binding domains and is different from the Rossmann dinucleotide\u2010binding fold. ApUp is bound in part by a long loop (residues 34\u201352) that crosses the active site. Several residues in the active site were previously identified as NAD\u2010binding residues. Glu 148, previously identified as playing a catalytic role in ADP\u2010ribosylation of elongation factor 2 by DT, is about 5 \u00c5 from uracil in ApUp. The trigger for insertion of the transmembrane domain of DT into the endosomal membrane at low pH may involve 3 intradomain and 4 interdomain salt bridges that will be weakened at low pH by protonation of their acidic residues. The refined model also reveals that each molecule in dimeric DT has an \u201copen\u201d structure unlike most globular proteins, which we call an open monomer. Two open monomers interact by \u201cdomain swapping\u201d to form a compact, globular dimeric DT structure. The possibility that the open monomer resembles a membrane insertion intermediate is discussed.<\/jats:p>","DOI":"10.1002\/pro.5560030911","type":"journal-article","created":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T01:57:19Z","timestamp":1234231039000},"page":"1444-1463","source":"Crossref","is-referenced-by-count":142,"title":["Refined structure of dimeric diphtheria toxin at 2.0 \u00c5 resolution"],"prefix":"10.1002","volume":"3","author":[{"given":"M. J.","family":"Bennett","sequence":"first","affiliation":[]},{"given":"S.","family":"Choe","sequence":"additional","affiliation":[]},{"given":"David","family":"Eisenberg","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2008,12,31]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/2271098a0"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.5.1320"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0079-6107(84)90007-5"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.8.3127"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560030912"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1107\/S056774088100561X"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00341a027"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1853201"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-0348-5419-1_2"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340030303"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/355472a0"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767390002355"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00357a019"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(88)65014-2"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.21.7237"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/357216a0"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.39.1.54-85.1975"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(85)90049-4"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb01822.x"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.1.172"},{"key":"e_1_2_1_22_1","first-page":"1504","article-title":"Attack by trypsin at a specific site within the intact toxin molecule","volume":"246","author":"Drazin R","year":"1971","journal-title":"J Biol Chem"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1016\/S0021-9258(19)77988-5","article-title":"The pH\u2010dependent conformational change of diphtheria toxin","volume":"263","author":"Dumont ME","year":"1988","journal-title":"J Biol Chem"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/319199a0"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(84)90309-7"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(89)90494-4"},{"key":"e_1_2_1_27_1","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1128\/jb.61.6.675-688.1951","article-title":"Studies on the virulence of bacteriophage\u2010infected strains of Corynebacterium diphtheriae.","volume":"61","author":"Freeman VJ","year":"1951","journal-title":"J Bacteriol"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(91)90577-S"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.22.6853"},{"key":"e_1_2_1_30_1","doi-asserted-by":"crossref","first-page":"6205","DOI":"10.1016\/S0021-9258(18)42682-8","article-title":"Structure of heparin\u2010binding EGF\u2010like growth factor","volume":"267","author":"Higashiyama S","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767392006044"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0108768187008632"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(88)90606-7"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360221211"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.8.4950"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3011.1989.tb01005.x"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00214a049"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(08)60608-7"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889891004399"},{"key":"e_1_2_1_40_1","volume-title":"Biochemistry","author":"Lehninger AL","year":"1975"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2795(73)90350-4"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(92)90033-7"},{"key":"e_1_2_1_43_1","doi-asserted-by":"crossref","first-page":"12016","DOI":"10.1016\/S0021-9258(19)70236-1","article-title":"Ligand interactions of diphtheria toxin: Relationships between the NAD site and the P site","volume":"255","author":"Lory S","year":"1980","journal-title":"J Biol Chem"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0365110X52002161"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90252-8"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2795(74)90246-3"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2795(77)90064-2"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/21.6.1369"},{"key":"e_1_2_1_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340120407"},{"key":"e_1_2_1_50_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1128\/iai.50.3.721-727.1985","article-title":"Receptor\u2010mediated entry of diphtheria toxin into monkey kidney (Vero) cells: Electron microscopic evaluation","volume":"50","author":"Morris RE","year":"1985","journal-title":"Infect Immunol"},{"key":"e_1_2_1_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90623-K"},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)52271-7"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)63870-0"},{"key":"e_1_2_1_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1987.tb13655.x"},{"key":"e_1_2_1_55_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.61.070192.001555"},{"key":"e_1_2_1_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(87)90358-5"},{"key":"e_1_2_1_57_1","doi-asserted-by":"crossref","first-page":"12025","DOI":"10.1016\/S0021-9258(19)70238-5","article-title":"Characterization and affinity labeling of the cationic phosphate\u2010binding (nucleotide binding) peptide located in the receptor\u2010binding region of the B\u2010fragment of diphtheria toxin","volume":"255","author":"Proia RL","year":"1980","journal-title":"J Biol Chem"},{"key":"e_1_2_1_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00339a019"},{"key":"e_1_2_1_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(08)60520-3"},{"key":"e_1_2_1_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(78)90201-2"},{"key":"e_1_2_1_61_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.87.3.828"},{"key":"e_1_2_1_62_1","doi-asserted-by":"crossref","first-page":"12352","DOI":"10.1016\/S0021-9258(18)37762-7","article-title":"Diphtheria toxin\u2010induced channels in Vero cells selective for monovalent cations","volume":"263","author":"Sandvig K","year":"1988","journal-title":"J Biol Chem"},{"key":"e_1_2_1_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(86)90245-7"},{"key":"e_1_2_1_64_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1172"},{"key":"e_1_2_1_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(76)90005-X"},{"key":"e_1_2_1_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/351371a0"},{"key":"e_1_2_1_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00007-1"},{"key":"e_1_2_1_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb00730.x"},{"key":"e_1_2_1_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.19.6014"},{"key":"e_1_2_1_70_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889890005568"},{"key":"e_1_2_1_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/newbio233008a0"},{"key":"e_1_2_1_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90209-7"},{"key":"e_1_2_1_73_1","doi-asserted-by":"crossref","first-page":"10710","DOI":"10.1016\/S0021-9258(19)70365-2","article-title":"ADP\u2010ribosylation of elongation factor 2 by diphtheria toxin","volume":"255","author":"Van Ness BG","year":"1980","journal-title":"J Biol Chem"},{"key":"e_1_2_1_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(91)90190-H"},{"key":"e_1_2_1_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/3.6.479"},{"key":"e_1_2_1_76_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0365110X49000813"},{"key":"e_1_2_1_77_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00489a021"},{"key":"e_1_2_1_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560030416"},{"key":"e_1_2_1_79_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00409a041"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpro.5560030911","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.5560030911","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T12:51:31Z","timestamp":1698151891000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.5560030911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,9]]},"references-count":78,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1994,9]]}},"alternative-id":["10.1002\/pro.5560030911"],"URL":"https:\/\/doi.org\/10.1002\/pro.5560030911","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,9]]}}}