{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T20:12:43Z","timestamp":1770063163090,"version":"3.49.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2015,1,8]],"date-time":"2015-01-08T00:00:00Z","timestamp":1420675200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1004021","type":"journal-article","created":{"date-parts":[[2015,1,8]],"date-time":"2015-01-08T19:07:44Z","timestamp":1420744064000},"page":"e1004021","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Novel Inhibitors Induce Large Conformational Changes of GAB1 Pleckstrin Homology Domain and Kill Breast Cancer Cells"],"prefix":"10.1371","volume":"11","author":[{"given":"Lu","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Du-Cuny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvestor","family":"Moses","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Dumas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuohe","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdol Hossein","family":"Rezaeian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Kuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle J.","family":"Meuillet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuxing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,1,8]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/S0962-8924(03)00002-3","article-title":"The Gab in signal transduction","volume":"13","author":"H Gu","year":"2003","journal-title":"Trends in Cell Biology"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/379560a0","article-title":"A Grb2-associated docking protein in EGF- and insulin-receptor signalling","volume":"379","author":"M Holgado-Madruga","year":"1996","journal-title":"Nature"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"9151","DOI":"10.1038\/sj.onc.1206983","article-title":"Epidermal growth factor receptor-dependent activation of Gab1 is involved in ErbB-2-mediated mammary tumor progression","volume":"22","author":"A Gillgrass","year":"2003","journal-title":"Oncogene"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1478-811X-7-22","article-title":"Function, regulation and pathological roles of the Gab\/DOS docking proteins","volume":"7","author":"FU Wohrle","year":"2009","journal-title":"Cell Commun Signal"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1111\/j.1349-7006.2003.tb01396.x","article-title":"The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors","volume":"94","author":"K Nishida","year":"2003","journal-title":"Cancer Science"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"12419","DOI":"10.1073\/pnas.94.23.12419","article-title":"Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor","volume":"94","author":"M Holgado-Madruga","year":"1997","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev.biophys.29.1.49","article-title":"Signaling and subcellular targeting by membrane-binding domains","volume":"29","author":"JH Hurley","year":"2000","journal-title":"Annu Rev Biophys Biomol Struct"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"31719","DOI":"10.1074\/jbc.274.44.31719","article-title":"A conserved inositol phospholipid binding site within the pleckstrin homology domain of the Gab1 docking protein is required for epithelial morphogenesis","volume":"274","author":"CR Maroun","year":"1999","journal-title":"Journal of Biological Chemistry"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1242\/jcs.037226","article-title":"A new mechanism for the regulation of Gab1 recruitment to the plasma membrane","volume":"122","author":"R Eulenfeld","year":"2009","journal-title":"Journal of Cell Science"},{"key":"ref10","first-page":"3231","article-title":"Simultaneous suppression of Erk and Akt\/PKB activation by a Gab1 pleckstrin homology (PH) domain decoy","volume":"23","author":"Y Ren","year":"2003","journal-title":"Anticancer Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0014-5793(01)03243-4","article-title":"Pleckstrin homology domains and the cytoskeleton","volume":"513","author":"MA Lemmon","year":"2002","journal-title":"FEBS Lett"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.cell.2013.06.048","article-title":"Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression","volume":"154","author":"CH Chan","year":"2013","journal-title":"Cell"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1056\/NEJMra1001389","article-title":"Triple-negative breast cancer","volume":"363","author":"WD Foulkes","year":"2010","journal-title":"N Engl J Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0022-2836(77)80200-3","article-title":"The Protein Data Bank: a computer-based archival file for macromolecular structures","volume":"112","author":"FC Bernstein","year":"1977","journal-title":"J Mol Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/bioinformatics\/17.4.377","article-title":"STRAP: editor for STRuctural Alignments of Proteins","volume":"17","author":"C Gille","year":"2001","journal-title":"Bioinformatics"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/bioinformatics\/16.4.404","article-title":"The PSIPRED protein structure prediction server","volume":"16","author":"LJ McGuffin","year":"2000","journal-title":"Bioinformatics"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.1091\/mbc.E11-04-0354","article-title":"Structural basis of the myosin X PH1(N)-PH2-PH1(C) tandem as a specific and acute cellular PI(3,4,5)P(3) sensor","volume":"22","author":"Q Lu","year":"2011","journal-title":"Mol Biol Cell"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"8378","DOI":"10.1073\/pnas.96.15.8378","article-title":"Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-PTB) targeting region of insulin receptor substrate 1","volume":"96","author":"S Dhe-Paganon","year":"1999","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1042\/bj3580287","article-title":"Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity","volume":"358","author":"CC Thomas","year":"2001","journal-title":"Biochem J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S1097-2765(00)00037-X","article-title":"Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains","volume":"6","author":"KM Ferguson","year":"2000","journal-title":"Mol Cell"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"W510","DOI":"10.1093\/nar\/gkp322","article-title":"QMEAN server for protein model quality estimation","volume":"37","author":"P Benkert","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"M Wiederstein","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: a program to check the stereochemical quality of protein structures","volume":"26","author":"RA Laskowski","year":"1993","journal-title":"J Appl Crystallogr"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0969-2126(99)80057-4","article-title":"Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol 1,3,4,5-tetrakisphosphate","volume":"7","author":"E Baraldi","year":"1999","journal-title":"Structure (London)"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/0092-8674(95)90219-8","article-title":"Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain","volume":"83","author":"KM Ferguson","year":"1995","journal-title":"Cell"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1021\/ci200271d","article-title":"A critical assessment of combined ligand- and structure-based approaches to HERG channel blocker modeling","volume":"51","author":"L Du-Cuny","year":"2011","journal-title":"J Chem Inf Model"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157489211793980079","article-title":"Recent development of anticancer therapeutics targeting Akt","volume":"6","author":"JK Morrow","year":"2011","journal-title":"Recent Pat Anticancer Drug Discov"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1016\/j.bmc.2011.01.049","article-title":"Development of sulfonamide AKT PH domain inhibitors","volume":"19","author":"AM Ahad","year":"2011","journal-title":"Bioorganic & Medicinal Chemistry"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1128\/MCB.21.15.5082-5093.2001","article-title":"Identification of insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the alpha6beta4 integrin-dependent activation of phosphoinositide 3-OH kinase and promotion of invasion","volume":"21","author":"LM Shaw","year":"2001","journal-title":"Mol Cell Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nsmb.2010","article-title":"The hidden energetics of ligand binding and activation in a glutamate receptor","volume":"18","author":"AY Lau","year":"2011","journal-title":"Nature Structural & Molecular Biology"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"6825","DOI":"10.1073\/pnas.0409005102","article-title":"Calculation of absolute protein-ligand binding free energy from computer simulations","volume":"102","author":"HJ Woo","year":"2005","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/prot.20033","article-title":"Exploring protein native states and large-scale conformational changes with a modified generalized born model","volume":"55","author":"A Onufriev","year":"2004","journal-title":"Proteins"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"13864","DOI":"10.1074\/jbc.M700505200","article-title":"Non-canonical interaction of phosphoinositides with pleckstrin homology domains of Tiam1 and ArhGAP9","volume":"282","author":"DF Ceccarelli","year":"2007","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1126\/science.1145720","article-title":"The genomic landscapes of human breast and colorectal cancers","volume":"318","author":"LD Wood","year":"2007","journal-title":"Science"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1126\/science.1141478","article-title":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling","volume":"316","author":"JA Engelman","year":"2007","journal-title":"Science"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1158\/1541-7786.MCR-06-0263","article-title":"Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines","volume":"5","author":"A Hollestelle","year":"2007","journal-title":"Mol Cancer Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1093\/jnci\/djr523","article-title":"Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome","volume":"104","author":"NT Ihle","year":"2012","journal-title":"J Natl Cancer Inst"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Bolton EE, Wang Y, Thiessen PA, Bryant SH (2008) Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities. In: Ralph AW, David, editors. Annual Reports in Computational Chemistry: Elsevier. pp. 217\u2013241.","DOI":"10.1016\/S1574-1400(08)00012-1"},{"key":"ref39","unstructured":"(2010) Suite 2010: LigPrep. 2.4 ed. New York, NY: Schrodinger, LLC."},{"key":"ref40","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids","volume":"118","author":"WL Jorgensen","year":"1996","journal-title":"Journal of the American Chemical Society"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"SF Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"6097","DOI":"10.1093\/nar\/18.20.6097","article-title":"Sequence logos: a new way to display consensus sequences","volume":"18","author":"TD Schneider","year":"1990","journal-title":"Nucleic Acids Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"D71","DOI":"10.1093\/nar\/gkr981","article-title":"Reorganizing the protein space at the Universal Protein Resource (UniProt)","volume":"40","author":"C Uniprot","year":"2012","journal-title":"Nucleic Acids Research"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modeling by satisfaction of spatial restraints","volume":"234","author":"A Sali","year":"1993","journal-title":"J Mol Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.bbalip.2006.04.008","article-title":"Membrane and juxtamembrane targeting by PH and PTB domains","volume":"1761","author":"JP DiNitto","year":"2006","journal-title":"Biochim Biophys Acta, Mol Cell Biol Lipids"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1110\/ps.062416606","article-title":"Statistical potential for assessment and prediction of protein structures","volume":"15","author":"MY Shen","year":"2006","journal-title":"Protein Sci"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"6983","DOI":"10.1016\/j.bmc.2009.08.022","article-title":"Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain","volume":"17","author":"L Du-Cuny","year":"2009","journal-title":"Bioorg Med Chem"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1097-2765(00)00038-1","article-title":"Structural basis of 3-phosphoinositide recognition by pleckstrin homology domains","volume":"6","author":"SE Lietzke","year":"2000","journal-title":"Mol Cell"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1158\/1535-7163.MCT-07-2276","article-title":"Discovery of a novel class of AKT pleckstrin homology domain inhibitors","volume":"7","author":"D Mahadevan","year":"2008","journal-title":"Mol Cancer Ther"},{"key":"ref50","first-page":"389","article-title":"Specific inhibition of the Akt1 pleckstrin homology domain by D-3-deoxy-phosphatidyl-myo-inositol analogues","volume":"2","author":"EJ Meuillet","year":"2003","journal-title":"Mol Cancer Ther"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"5073","DOI":"10.1158\/0008-5472.CAN-08-3839","article-title":"In Vitro and In Vivo Activity of a Novel Small Molecule Inhibitor Targeting the Pleckstrin Homology Domain of Protein Kinase B\/AKT","volume":"69","author":"S Moses","year":"2009","journal-title":"Cancer Research"},{"key":"ref52","unstructured":"Case DA, Darden TA, Cheatham TE, Simmerling CL, Wang J, et al. (2012) AMBER 12."},{"key":"ref53","unstructured":"(2007) GOLD 5.1. 5.1 ed. Cambridge, UK: CCDC."},{"key":"ref54","unstructured":"(2004) GRID v22c. Perugia, Italy: Molecular Discovery Ltd."},{"key":"ref55","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1021\/ci600253e","article-title":"A common reference framework for analyzing\/comparing proteins and ligands. Fingerprints for Ligands and Proteins (FLAP): theory and application","volume":"47","author":"M Baroni","year":"2007","journal-title":"J Chem Inf Model"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T08:49:12Z","timestamp":1589014152000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004021"}},"subtitle":[],"editor":[{"given":"Michael","family":"Gilson","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,1,8]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,1,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1004021","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,8]]}}}