{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:52:31Z","timestamp":1790401951562,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,7,20]],"date-time":"2009-07-20T00:00:00Z","timestamp":1248048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oxidative stress is a widespread challenge for living organisms, and especially so for parasitic ones, given the fact that their hosts can produce reactive oxygen species (ROS) as a mechanism of defense. Thus, long lived parasites, such as the flatworm Schistosomes, have evolved refined enzymatic systems capable of detoxifying ROS. Among these, glutathione peroxidases (Gpx) are a family of sulfur or selenium\u2010dependent isozymes sharing the ability to reduce peroxides using the reducing equivalents provided by glutathione or possibly small proteins such as thioredoxin. As for other frontline antioxidant enzymatic systems, Gpxs are localized in the tegument of the Schistosomes, the outermost defense layer. In this article, we present the first crystal structure at 1.0 and 1.7 \u00c5 resolution of two recombinant SmGpxs, carrying the active site mutations Sec43Cys and Sec43Ser, respectively. The structures confirm that this enzyme belongs to the monomeric class 4 (phospholipid hydroperoxide) Gpx. In the case of the Sec to Cys mutant, the catalytic Cys residue is oxidized to sulfonic acid. By combining static crystallography with molecular dynamics simulations, we obtained insight into the substrate binding sites and the conformational changes relevant to catalysis, proposing a role for the unusual reactivity of the catalytic residue. Proteins 2010. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.22536","type":"journal-article","created":{"date-parts":[[2009,7,21]],"date-time":"2009-07-21T10:09:18Z","timestamp":1248170958000},"page":"259-270","source":"Crossref","is-referenced-by-count":36,"title":["Combining crystallography and molecular dynamics: The case of\n                    <i>Schistosoma mansoni<\/i>\n                    phospholipid glutathione peroxidase"],"prefix":"10.1002","volume":"78","author":[{"given":"Daniela","family":"Dimastrogiovanni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Anselmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Erica","family":"Miele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Boumis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linn","family":"Petersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Angelucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo Di","family":"Nola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Brunori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bellelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,8,27]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2008.06542.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000664"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05774.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1528"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.38"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2005.11.007"},{"key":"e_1_2_6_8_2","first-page":"118","article-title":"Probing the presumed catalytic triad of a selenium\u2010containing peroxidase by mutational analysis","volume":"37","author":"Maiorino M","year":"1998","journal-title":"Z Ernahrungswiss"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8223(99)00198-4"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503638200"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1983.tb07429.x"},{"key":"e_1_2_6_12_2","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1016\/S0021-9258(18)53812-6","article-title":"Expression, characterization and tissue distribution of a new cellular selenium\u2010dependent glutathione peroxidase, GSHPx\u2010GI","volume":"268","author":"Chu FF","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.1005"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0838w.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2055"},{"key":"e_1_2_6_16_2","first-page":"412","article-title":"Purification and physicochemical characterization of a recombinant phospholipid hydroperoxide glutathione peroxidase from Oriza sativa","volume":"40","author":"Wang Z","year":"2007","journal-title":"J Biochem Mol Biol"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2007.130"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.41.29294"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5432.1393"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.9.4653"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi700840d"},{"key":"e_1_2_6_22_2","unstructured":"JohanssonC KavanaghKL RojkovaA GileadiO Von DelftF ArrowsmithC WeigeltJ SundstromM EdwardsA OppermannU.Structural genomics consortium (SGC). Crystal structure of the selenocysteine to glycine mutant of human glutathione peroxidase 4(GPX4)in press."},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-4758(97)01141-1"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182007002600"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182004004895"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.05.002"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21986"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/biof.5520270110"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512601200"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90798-6"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(92)90042-I"},{"key":"e_1_2_6_32_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1006\/expr.1995.1038","article-title":"Schistosoma mansoni: cloning the gene encoding glutathione peroxidase","volume":"80","author":"Mei H","year":"1995","journal-title":"Exp Parasitol"},{"key":"e_1_2_6_33_2","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1128\/iai.64.10.4299-4306.1996","article-title":"Expression and characterization of glutathione peroxidase activity in the human blood fluke Schistosoma mansoni","volume":"64","author":"Mei H","year":"1996","journal-title":"Infect Immun"},{"key":"e_1_2_6_34_2","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1110\/ps.073096508","article-title":"Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid protein","volume":"17","author":"Salisbury FR","year":"2008","journal-title":"Protein Sci"},{"key":"e_1_2_6_35_2","first-page":"1373","article-title":"The CCP4 Suite: programs for protein crystallography","volume":"57","author":"Collaborative Computational Project, Number 4","year":"1994","journal-title":"Acta Crystallogr Sect D"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904023716"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm216"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889892009944"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm404"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.464913"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevB.37.785"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.463096"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540141112"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540110311"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-1280(89)87088-5"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-015-7658-1_21"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-4655(95)00042-E"},{"key":"e_1_2_6_49_2","volume-title":"Biomolecular simulations: the GROMOS96 manual and user guide","author":"Van Gunsteren WF","year":"1996"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H"},{"key":"e_1_2_6_51_2","first-page":"9","article-title":"Molecular dynamics simulations with constrained roto\u2010translational motions: theoretical basis and statistical mechanical consistency","volume":"112","author":"Amadei A","year":"2000","journal-title":"JChem Phys"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-244090-8.50009-6"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.470117"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340170408"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/0263-7855(95)00073-9"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki481"},{"key":"e_1_2_6_57_2","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1089\/ars.2008.2057","article-title":"Evolutionary and structural insights into the multifaceted glutathione peroxidase (Gpx) superfamily","volume":"10","author":"Toppo S","year":"2008","journal-title":"Antioxid Redox Signal"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(01)00154-X"},{"key":"e_1_2_6_59_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1590\/S0074-02762004000900007","article-title":"Vaccination with antioxidant enzymes confers protective immunity against challenge infection with Schistosoma mansoni","volume":"99","author":"Lo Verde PT","year":"2004","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"e_1_2_6_60_2","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/S0021-9258(19)40252-4","article-title":"Protective action of PhGPX against membrane\u2010damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides","volume":"265","author":"Thomas JP","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_6_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(97)00091-1"},{"key":"e_1_2_6_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi050815q"},{"key":"e_1_2_6_63_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02536034"},{"key":"e_1_2_6_64_2","doi-asserted-by":"publisher","DOI":"10.1006\/expr.1997.4150"},{"key":"e_1_2_6_65_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp0016683"}],"container-title":["Proteins: Structure, Function, and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprot.22536","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prot.22536","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T09:04:20Z","timestamp":1697360660000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prot.22536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,27]]},"references-count":64,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,2]]}},"alternative-id":["10.1002\/prot.22536"],"URL":"https:\/\/doi.org\/10.1002\/prot.22536","archive":["Portico"],"relation":{},"ISSN":["0887-3585","1097-0134"],"issn-type":[{"value":"0887-3585","type":"print"},{"value":"1097-0134","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,27]]}}}