{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:03:02Z","timestamp":1790010182219,"version":"4.0.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,5,22]]},"abstract":"<jats:p>\n                    The Ras family of GTPases is a collection of molecular switches\n that link receptors on the plasma membrane to signaling pathways that\n regulate cell proliferation and differentiation. The accessory\n GTPase-activating proteins (GAPs) negatively regulate the cell\n signaling by increasing the slow intrinsic GTP to GDP hydrolysis rate\n of Ras. Mutants of Ras are found in 25\u201330% of human tumors. The most\n dramatic property of these mutants is their insensitivity to the\n negative regulatory action of GAPs. All known oncogenic mutants of Ras\n map to a small subset of amino acids. Gln-61 is particularly important\n because virtually all mutations of this residue eliminate sensitivity\n to GAPs. Despite its obvious importance for carcinogenesis, the role of\n Gln-61 in the GAP-stimulated GTPase activity of Ras has remained a\n mystery. Our molecular dynamics simulations of the p21ras\u2013p120GAP\u2013GTP\n complex suggest that the local structure around the catalytic region\n can be different from that revealed by the x-ray crystal structure. We\n find that the carbonyl oxygen on the backbone of the arginine finger\n supplied in trans by p120GAP (Arg-789) interacts with a water molecule\n in the active site that is forming a bridge between the NH\n                    <jats:sub>2<\/jats:sub>\n                    group of the Gln-61 and the \u03b3-phosphate of GTP. Thus, Arg-789 may\n play a dual role in generating the nucleophile as well as stabilizing\n the transition state for P\u2014O bond cleavage.\n                  <\/jats:p>","DOI":"10.1073\/pnas.091506998","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"6033-6038","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["The arginine finger of RasGAP helps Gln-61 align the nucleophilic water in GAP-stimulated hydrolysis of GTP"],"prefix":"10.1073","volume":"98","author":[{"given":"Haluk","family":"Resat","sequence":"first","affiliation":[{"name":"Pacific Northwest National Laboratory, Richland, WA 99352"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. P.","family":"Straatsma","sequence":"additional","affiliation":[{"name":"Pacific Northwest National Laboratory, Richland, WA 99352"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Pacific Northwest National Laboratory, Richland, WA 99352"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Miller","sequence":"additional","affiliation":[{"name":"Pacific Northwest National Laboratory, Richland, WA 99352"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,5,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/348125a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/349117a0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.62.070193.004223"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0898-6568(94)90030-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0195-3"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8160"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.10.12.8903506"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201259"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.14.5026"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/351576a0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.12.5.2050-2056.1992"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)74211-2"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.56.070187.004023"},{"key":"e_1_3_3_14_2","first-page":"4682","volume":"49","author":"Bos J","year":"1989","unstructured":"J Bos Cancer Res 49, 4682\u20134689 (1989).","journal-title":"Cancer Res"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8430333"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00152a002"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2821624"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0195-36"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb07409.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90018-A"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.8.3649"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0794-476"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/372276a0"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0997-686"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi000640e"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5324.333"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540040211"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1301"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-4655(95)00043-F"},{"key":"e_1_3_3_30_2","volume-title":"nwchem, A Computational Chemistry Package for Parallel Computers","author":"Harrison R J","year":"2000","unstructured":"R J Harrison, J A Nichols, T P Straatsma, M Dupuis, E J Bylaska, G I Fann, T L Windus, E Apra, J Anchell, D Bernholdt, et al. nwchem, A Computational Chemistry Package for Parallel Computers (Pacific Northwest National Laboratory, Richland, WA, , Version 4.0. (2000)."},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00124a002"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00136a005"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00177a014"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00037a047"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.22.11905"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8073283"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5271.115"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00532-3"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.091506998","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:22:35Z","timestamp":1649787755000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.091506998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5,22]]},"references-count":38,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2001,5,22]]}},"alternative-id":["10.1073\/pnas.091506998"],"URL":"https:\/\/doi.org\/10.1073\/pnas.091506998","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5,22]]},"assertion":[{"value":"2000-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-05-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}