{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:06:11Z","timestamp":1790431571024,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,7,6]],"date-time":"2009-07-06T00:00:00Z","timestamp":1246838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The National Scientific Research Centre"},{"name":"Pasteur Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Edema Factor (EF), one of the virulence factors of anthrax, is an adenylyl cyclase that promotes the overproduction of cyclic\u2010AMP (cAMP) from ATP, and therefore perturbs cell signaling. Crystallographic structures of EF bound to ATP analogs and reaction products, cyclic\u2010AMP, and Pyrophosphate (PPi), revealed different substrate conformations and catalytic\u2010cation binding modes, one or two cations being observed in the active site. To shed light into the biological significance of these crystallographic structures, the energetics, geometry, and dynamics of the active site are analyzed using molecular dynamics simulations. The ATP conformation observed in the one\u2010metal\u2010ion structure allows stronger interactions with the catalytic ion, and ATP is more restrained than in the structure containing two Mg<jats:sup>2+<\/jats:sup> ions. Therefore, we propose that the conformation observed in the one\u2010ion crystal structure is a more probable starting point for the reaction. The simulations also suggest that a C3\u2032\u2010endo sugar pucker facilitates nucleophilic attack. Additionally, the two\u2010cation binding mode restrains the mobility of the reaction products, and thus their tendency to dissociate. Proteins 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.22523","type":"journal-article","created":{"date-parts":[[2009,7,7]],"date-time":"2009-07-07T02:31:15Z","timestamp":1246933875000},"page":"971-983","source":"Crossref","is-referenced-by-count":15,"title":["ATP conformations and ion binding modes in the active site of anthrax edema factor: A computational analysis"],"prefix":"10.1002","volume":"77","author":[{"given":"Leandro","family":"Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Laine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Th\u00e9r\u00e8se E.","family":"Malliavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Nilges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Blondel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,8,24]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/415396a"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf681"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600574"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21862"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402689200"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.07.045"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.756"},{"key":"e_1_2_7_9_2","doi-asserted-by":"crossref","first-page":"8595","DOI":"10.1016\/S0021-9258(18)93016-4","article-title":"Expression and characterization of calmodulin\u2010activated (type i) adenylyl cyclase","volume":"266","author":"Tang WJ","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21249"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp973084f"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(19970130)18:2<221::AID-JCC7>3.0.CO;2-X"},{"key":"e_1_2_7_13_2","volume-title":"Gaussian 03, Revision C02","author":"Frisch MJ","year":"2004"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.445869"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10216"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21224"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20289"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9991(77)90098-5"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(96)00018-5"},{"key":"e_1_2_7_20_2","volume-title":"The pymol molecular graphics system","author":"DeLano WL","year":"2002"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767388010128"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00778a043"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja981844"},{"key":"e_1_2_7_24_2","volume-title":"AMBER 9","author":"Case DA","year":"2006"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21123"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10262"}],"container-title":["Proteins: Structure, Function, and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprot.22523","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprot.22523","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prot.22523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:28:17Z","timestamp":1697502497000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prot.22523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,24]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["10.1002\/prot.22523"],"URL":"https:\/\/doi.org\/10.1002\/prot.22523","archive":["Portico"],"relation":{},"ISSN":["0887-3585","1097-0134"],"issn-type":[{"value":"0887-3585","type":"print"},{"value":"1097-0134","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,24]]}}}