{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:22:48Z","timestamp":1777652568306,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T00:00:00Z","timestamp":1239580800000},"content-version":"vor","delay-in-days":2628,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2002,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Yersinia pestis<\/jats:italic>, the causative agent of bubonic plague, evades the immune response of the infected organism by using a type III (contact\u2010dependent) secretion system to deliver effector proteins into the cytosol of mammalian cells, where they interfere with signaling pathways that regulate inflammation and cytoskeleton dynamics. The cytotoxic effector YopE functions as a potent GTPase\u2010activating protein (GAP) for Rho family GTP\u2010binding proteins, including RhoA, Rac1, and Cdc42. Down\u2010regulation of these molecular switches results in the loss of cell motility and inhibition of phagocytosis, enabling <jats:italic>Y. pestis<\/jats:italic> to thrive on the surface of macrophages. We have determined the crystal structure of the GAP domain of YopE (YopE<jats:sub>GAP<\/jats:sub>; residues 90\u2013219) at 2.2\u2010\u00c5 resolution. Apart from the fact that it is composed almost entirely of \u03b1\u2010helices, YopE<jats:sub>GAP<\/jats:sub> shows no obvious structural similarity with eukaryotic RhoGAP domains. Moreover, unlike the catalytically equivalent arginine fingers of the eukaryotic GAPs, which are invariably contained within flexible loops, the critical arginine in YopE<jats:sub>GAP<\/jats:sub> (Arg144) is part of an \u03b1\u2010helix. The structure of YopE<jats:sub>GAP<\/jats:sub> is strikingly similar to the GAP domains from <jats:italic>Pseudomonas aeruginosa<\/jats:italic> (ExoS<jats:sub>GAP<\/jats:sub>) and <jats:italic>Salmonella enterica<\/jats:italic> (SptP<jats:sub>GAP<\/jats:sub>), despite the fact that the three amino acid sequences are not highly conserved. A comparison of the YopE<jats:sub>GAP<\/jats:sub> structure with those of the Rac1\u2010ExoS<jats:sub>GAP<\/jats:sub> and Rac1\u2010SptP complexes indicates that few, if any, significant conformational changes occur in YopE<jats:sub>GAP<\/jats:sub> when it interacts with its G protein targets. The structure of YopE<jats:sub>GAP<\/jats:sub> may provide an avenue for the development of novel therapeutic agents to combat plague.<\/jats:p>","DOI":"10.1110\/ps.34102","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T23:59:58Z","timestamp":1027727998000},"page":"401-408","source":"Crossref","is-referenced-by-count":55,"title":["Crystal structure of the <i>Yersinia pestis<\/i> GTPase activator YopE"],"prefix":"10.1002","volume":"11","author":[{"given":"Artem G.","family":"Evdokimov","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph E.","family":"Tropea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen M.","family":"Routzahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Waugh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,4,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00422-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(97)01067-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.02021.x"},{"key":"e_1_2_7_6_1","first-page":"34","article-title":"\u201cdm\u201d: An automated procedure for phase improvement by density modification","volume":"31","author":"Cowtan K.","year":"1994","journal-title":"Joint CCP4 and ESF\u2010EACBM Newsletter on Protein Crystallography"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(97)76075-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444900013378"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(97)76073-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/45829"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)80008-3"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.51.36369"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5350.509"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)80010-1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1489"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889891004430"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767390010224"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/prep.2000.1251"},{"key":"e_1_2_7_19_1","first-page":"9","article-title":"A super position","volume":"31","author":"Kleywegt G.J.","year":"1994","journal-title":"Joint CCP4 and ESF\u2010EACBM Newsletter on Protein Crystallography"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.10.6066-6068.2000"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2000.tb09159.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1128\/jb.179.5.1609-1613.1997","article-title":"Biochemical relationships between the 53\u2010kilodalton (Exo53) and 49\u2010kilodalton (ExoS) forms of exoenzyme S of Pseudomonas aeruginosa.","volume":"179","author":"Liu S.","year":"1997","journal-title":"J. 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