{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:59:08Z","timestamp":1790884748449,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2008,2,28]],"date-time":"2008-02-28T00:00:00Z","timestamp":1204156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2008,2,28]],"date-time":"2008-02-28T00:00:00Z","timestamp":1204156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"published-print":{"date-parts":[[2008,4,9]]},"DOI":"10.1038\/emboj.2008.30","type":"journal-article","created":{"date-parts":[[2008,2,28]],"date-time":"2008-02-28T09:15:08Z","timestamp":1204190108000},"page":"1145-1153","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["The Rap\u2013RapGAP complex: GTP hydrolysis without catalytic glutamine and arginine residues"],"prefix":"10.1038","volume":"27","author":[{"given":"Andrea","family":"Scrima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"Deaconescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Wittinghofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2008,2,28]]},"reference":[{"key":"BFEMBJ200830_CR1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nsb0997-686","volume":"4","author":"MR Ahmadian","year":"1997","unstructured":"Ahmadian MR, Stege P, Scheffzek K, Wittinghofer A (1997) Confirmation of the arginine\u2010finger hypothesis for the GAP\u2010stimulated GTP\u2010hydrolysis reaction of Ras. Nat Struct Biol 4: 686\u2013689","journal-title":"Nat Struct Biol"},{"key":"BFEMBJ200830_CR2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nature01040","volume":"419","author":"X Bi","year":"2002","unstructured":"Bi X, Corpina RA, Goldberg J (2002) Structure of the Sec23\/24\u2010Sar1 pre\u2010budding complex of the COPII vesicle coat. Nature 419: 271\u2013277","journal-title":"Nature"},{"key":"BFEMBJ200830_CR3","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/35073073","volume":"2","author":"JL Bos","year":"2001","unstructured":"Bos JL, de Rooij J, Reedquist KA (2001) Rap1 signalling: adhering to new models. Nat Rev Mol Cell Biol 2: 369\u2013377","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFEMBJ200830_CR4","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.cell.2007.05.018","volume":"129","author":"JL Bos","year":"2007","unstructured":"Bos JL, Rehmann H, Wittinghofer A (2007) GEFs and GAPs: critical elements in the control of small G proteins. Cell 129: 865\u2013877","journal-title":"Cell"},{"key":"BFEMBJ200830_CR5","doi-asserted-by":"crossref","first-page":"12525","DOI":"10.1074\/jbc.M109176200","volume":"277","author":"T Brinkmann","year":"2002","unstructured":"Brinkmann T, Daumke O, Herbrand U, K\u00fchlmann D, Stege P, Ahmadian MR, Wittinghofer A (2002) Rap\u2010specific GTPase activating protein follows an alternative mechanism. J Biol Chem 277: 12525\u201312531","journal-title":"J Biol Chem"},{"key":"BFEMBJ200830_CR6","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1107\/S0907444998003254","volume":"54","author":"AT Brunger","year":"1998","unstructured":"Brunger AT, Adams PD, Clore GM, DeLano WL, Gros P, Grosse\u2010Kunstleve RW, Jiang JS, Kuszewski J, Nilges M, Pannu NS, Read RJ, Rice LM, Simonson T, Warren GL (1998) Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr D 54: 905\u2013921","journal-title":"Acta Crystallogr D"},{"key":"BFEMBJ200830_CR7","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.jmb.2006.11.022","volume":"367","author":"PP Chakrabarti","year":"2007","unstructured":"Chakrabarti PP, Daumke O, Suveyzdis Y, K\u00f6tting C, Gerwert K, Wittinghofer A (2007) Insight into catalysis of a unique GTPase reaction by a combined biochemical and FTIR approach. J Mol Biol 367: 983\u2013995","journal-title":"J Mol Biol"},{"key":"BFEMBJ200830_CR8","doi-asserted-by":"crossref","first-page":"5582","DOI":"10.1093\/emboj\/16.18.5582","volume":"16","author":"J Cherfils","year":"1997","unstructured":"Cherfils J, Menetrey J, Le Bras G, Janoueix\u2010Lerosey I, de Gunzburg J, Garel JR, Auzat I (1997) Crystal structures of the small G protein Rap2A in complex with its substrate GTP, with GDP and with GTPgammaS. EMBO J 16: 5582\u20135591","journal-title":"EMBO J"},{"key":"BFEMBJ200830_CR9","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature02505","volume":"429","author":"O Daumke","year":"2004","unstructured":"Daumke O, Weyand M, Chakrabarti PP, Vetter IR, Wittinghofer A (2004) The GTPase\u2010activating protein Rap1GAP uses a catalytic asparagine. Nature 429: 197\u2013201","journal-title":"Nature"},{"key":"BFEMBJ200830_CR10","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S0022-2836(03)00947-1","volume":"332","author":"T Daviter","year":"2003","unstructured":"Daviter T, Wieden HJ, Rodnina MV (2003) Essential role of histidine 84 in elongation factor Tu for the chemical step of GTP hydrolysis on the ribosome. J Mol Biol 332: 689\u2013699","journal-title":"J Mol Biol"},{"key":"BFEMBJ200830_CR11","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/S1097-2765(03)00220-X","volume":"11","author":"A Garami","year":"2003","unstructured":"Garami A, Zwartkruis FJ, Nobukuni T, Joaquin M, Rocciom M, Stocker H, Kozma SC, Hafen E, Bos JL, Thomas G (2003) Insulin activation of Rheb, a mediator of mTOR\/S6K\/4E\u2010BP signaling, is inhibited by TSC1 and 2. Mol Cell 11: 1457\u20131466","journal-title":"Mol Cell"},{"key":"BFEMBJ200830_CR12","doi-asserted-by":"crossref","first-page":"27492","DOI":"10.1074\/jbc.M600809200","volume":"281","author":"R Gasper","year":"2006","unstructured":"Gasper R, Scrima A, Wittinghofer A (2006) Structural insights into HypB, a GTP\u2010binding protein that regulates metal binding. J Biol Chem 281: 27492\u201327502","journal-title":"J Biol Chem"},{"key":"BFEMBJ200830_CR13","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature04510","volume":"440","author":"A Ghosh","year":"2006","unstructured":"Ghosh A, Praefcke GJ, Renault L, Wittinghofer A, Herrmann C (2006) How guanylate\u2010binding proteins achieve assembly\u2010stimulated processive cleavage of GTP to GMP. Nature 440: 101\u2013104","journal-title":"Nature"},{"key":"BFEMBJ200830_CR14","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1021\/bi9821770","volume":"38","author":"DL Graham","year":"1999","unstructured":"Graham DL, Eccleston JF, Lowe PN (1999) The conserved arginine in rho\u2010GTPase\u2010activating protein is essential for efficient catalysis but not for complex formation with Rho.GDP and aluminium fluoride. Biochemistry 38: 985\u2013991","journal-title":"Biochemistry"},{"key":"BFEMBJ200830_CR15","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/jb\/mvg180","volume":"134","author":"M Hattori","year":"2003","unstructured":"Hattori M, Minato N (2003) Rap1 GTPase: functions, regulation, and malignancy. J Biochem (Tokyo) 134: 479\u2013484","journal-title":"J Biochem (Tokyo)"},{"key":"BFEMBJ200830_CR16","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1101\/gad.1110003","volume":"17","author":"K Inoki","year":"2003","unstructured":"Inoki K, Li Y, Xu T, Guan KL (2003) Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 17: 1829\u20131834","journal-title":"Genes Dev"},{"key":"BFEMBJ200830_CR17","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1107\/S0021889893005588","volume":"26","author":"W Kabsch","year":"1993","unstructured":"Kabsch W (1993) Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J Appl Cryst 26: 795\u2013800","journal-title":"J Appl Cryst"},{"key":"BFEMBJ200830_CR18","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0022-2836(02)01136-1","volume":"324","author":"A Kraemer","year":"2002","unstructured":"Kraemer A, Brinkmann T, Plettner I, Goody R, Wittinghofer A (2002) Fluorescently labelled guanine nucleotide binding proteins to analyse elementary steps of GAP\u2010catalysed reactions. J Mol Biol 324: 763\u2013774","journal-title":"J Mol Biol"},{"key":"BFEMBJ200830_CR19","doi-asserted-by":"crossref","first-page":"9891","DOI":"10.1074\/jbc.M512802200","volume":"281","author":"S Kupzig","year":"2006","unstructured":"Kupzig S, Deaconescu D, Bouyoucef D, Walker SA, Liu Q, Polte CL, Daumke O, Ishizaki T, Lockyer PJ, Wittinghofer A, Cullen PJ (2006) GAP1 family members constitute bifunctional Ras and Rap GTPase\u2010activating proteins. J Biol Chem 281: 9891\u20139900","journal-title":"J Biol Chem"},{"key":"BFEMBJ200830_CR20","doi-asserted-by":"crossref","first-page":"7965","DOI":"10.1128\/MCB.24.18.7965-7975.2004","volume":"24","author":"Y Li","year":"2004","unstructured":"Li Y, Inoki K, Guan KL (2004) Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol 24: 7965\u20137975","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ200830_CR21","doi-asserted-by":"crossref","first-page":"8160","DOI":"10.1073\/pnas.93.16.8160","volume":"93","author":"KA Maegley","year":"1996","unstructured":"Maegley KA, Admiraal SJ, Herschlag D (1996) Ras\u2010catalyzed hydrolysis of GTP: a new perspective from model studies. Proc Natl Acad Sci USA 93: 8160\u20138166","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ200830_CR22","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1006\/jsbi.1999.4094","volume":"125","author":"DE McRee","year":"1999","unstructured":"McRee DE (1999) XtalView\/Xfit\u2014a versatile program for manipulating atomic coordinates and electron density. J Struct Biol 125: 156\u2013165","journal-title":"J Struct Biol"},{"key":"BFEMBJ200830_CR23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1107\/S0907444996012255","volume":"53","author":"GN Murshudov","year":"1997","unstructured":"Murshudov GN, Vagin AA, Dodson EJ (1997) Refinement of macromolecular structures by the maximum\u2010likelihood method. Acta Cryst D 53: 240\u2013255","journal-title":"Acta Cryst D"},{"key":"BFEMBJ200830_CR24","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/4156","volume":"5","author":"N Nassar","year":"1998","unstructured":"Nassar N, Hoffman GR, Manor D, Clardy JC, Cerione RA (1998) Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP. Nat Struct Biol 5: 1047\u20131052","journal-title":"Nat Struct Biol"},{"key":"BFEMBJ200830_CR25","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nsb0896-723","volume":"3","author":"N Nassar","year":"1996","unstructured":"Nassar N, Horn G, Herrmann C, Block C, Janknecht R, Wittinghofer A (1996) Ras\/Rap effector specificity determined by charge reversal. Nat Struct Biol 3: 723\u2013729","journal-title":"Nat Struct Biol"},{"key":"BFEMBJ200830_CR26","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/0470869976.ch9","volume":"262","author":"T Nobukini","year":"2004","unstructured":"Nobukini T, Thomas G (2004) The mTOR\/S6K signalling pathway: the role of the TSC1\/2 tumour suppressor complex and the proto\u2010oncogene Rheb. Novartis Found Symp 262: 148\u2013154","journal-title":"Novartis Found Symp"},{"key":"BFEMBJ200830_CR27","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/nature04847","volume":"442","author":"X Pan","year":"2006","unstructured":"Pan X, Eathiraj S, Munson M, Lambright DG (2006) TBC\u2010domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual\u2010finger mechanism. Nature 442: 303\u2013306","journal-title":"Nature"},{"key":"BFEMBJ200830_CR28","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/39651","volume":"389","author":"K Rittinger","year":"1997","unstructured":"Rittinger K, Walker PA, Eccleston JF, Smerdon SJ, Gamblin SJ (1997) Structure at 1.65 \u00c5 of RhoA and its GTPase\u2010activating protein in complex with a transition\u2010state analogue. Nature 389: 758\u2013762","journal-title":"Nature"},{"key":"BFEMBJ200830_CR29","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1126\/science.277.5324.333","volume":"277","author":"K Scheffzek","year":"1997","unstructured":"Scheffzek K, Ahmadian MR, Kabsch W, Wiesmuller L, Lautwein A, Schmitz F, Wittinghofer A (1997) The Ras\u2010RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science 277: 333\u2013338","journal-title":"Science"},{"key":"BFEMBJ200830_CR30","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1038\/sj.emboj.7601171","volume":"25","author":"A Scrima","year":"2006","unstructured":"Scrima A, Wittinghofer A (2006) Dimerisation\u2010dependent GTPase reaction of MnmE: how potassium acts as GTPase\u2010activating element. EMBO J 25: 2940\u20132951","journal-title":"EMBO J"},{"key":"BFEMBJ200830_CR31","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/415662a","volume":"415","author":"MJ Seewald","year":"2002","unstructured":"Seewald MJ, K\u00f6rner C, Wittinghofer A, Vetter IR (2002) RanGAP mediates GTP hydrolysis without an arginine finger. Nature 415: 662\u2013666","journal-title":"Nature"},{"key":"BFEMBJ200830_CR32","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/S0960-9822(03)00506-2","volume":"13","author":"AR Tee","year":"2003","unstructured":"Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J (2003) Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase\u2010activating protein complex toward Rheb. Curr Biol 13: 1259\u20131268","journal-title":"Curr Biol"},{"key":"BFEMBJ200830_CR33","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1107\/S0021889897006766","volume":"30","author":"A Vagin","year":"1997","unstructured":"Vagin A, Teplyakov A (1997) MOLREP: an automated program for molecular replacement. J Appl Cryst 30: 1022\u20131025","journal-title":"J Appl Cryst"},{"key":"BFEMBJ200830_CR34","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1126\/science.1062023","volume":"294","author":"IR Vetter","year":"2001","unstructured":"Vetter IR, Wittinghofer A (2001) The guanine nucleotide\u2010binding switch in three dimensions. Science 294: 1299\u20131304","journal-title":"Science"},{"key":"BFEMBJ200830_CR35","doi-asserted-by":"crossref","first-page":"17093","DOI":"10.1074\/jbc.M501253200","volume":"280","author":"Y Yu","year":"2005","unstructured":"Yu Y, Li S, Xu X, Li Y, Guan K, Arnold E, Ding J (2005) Structural basis for the unique biological function of small GTPase RHEB. J Biol Chem 280: 17093\u201317100","journal-title":"J Biol Chem"},{"key":"BFEMBJ200830_CR36","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/ncb999","volume":"5","author":"Y Zhang","year":"2003","unstructured":"Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D (2003) Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol 5: 578\u2013581","journal-title":"Nat Cell Biol"}],"container-title":["The EMBO Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Femboj.2008.30","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/emboj.2008.30.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1038\/emboj.2008.30","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1038\/emboj.2008.30","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/emboj.2008.30.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:52:17Z","timestamp":1779234737000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1038\/emboj.2008.30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,28]]},"references-count":36,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2008,4,9]]}},"alternative-id":["BFEMBJ200830"],"URL":"https:\/\/doi.org\/10.1038\/emboj.2008.30","relation":{},"ISSN":["0261-4189","1460-2075"],"issn-type":[{"value":"0261-4189","type":"print"},{"value":"1460-2075","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,28]]},"assertion":[{"value":"22 November 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 February 2008","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2008","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}