{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T16:44:51Z","timestamp":1771001091618,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,2,7]],"date-time":"2008-02-07T00:00:00Z","timestamp":1202342400000},"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":[[2008,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tuberculosis (TB) remains the leading cause of mortality due to a single bacterial pathogen, Mycobacterium tuberculosis. The reemergence of TB as a potential public health threat, the high susceptibility of human immunodeficiency virus\u2010infected persons to the disease, the proliferation of multi\u2010drug\u2010resistant strains (MDR\u2010TB) and, more recently, of extensively drug resistant isolates (XDR\u2010TB) have created a need for the development of new antimycobacterial agents. Amongst the several proteins and\/or enzymes to be studied as potential targets to develop novel drugs against M. tuberculosis, the enzymes of the shikimate pathway are attractive targets because they are essential in algae, higher plants, bacteria, and fungi, but absent from mammals. The mycobacterial shikimate pathway leads to the biosynthesis of chorismate, which is a precursor of aromatic amino acids, naphthoquinones, menaquinones, and mycobactins. Here we report the structural studies by homology modeling and circular dichroism spectroscopy of the shikimate dehydrogenase from M. tuberculosis (MtSDH), which catalyses the fourth step of the shikimate pathway. Our structural models show that the MtSDH has similar structure to other shikimate dehydrogenase structures previously reported either in presence or absence of NADP, despite the low amino acid sequence identity. The circular dichroism spectra corroborate the secondary structure content observed in the MtSDH models developed. The enzyme was stable up to 50\u00b0C presenting a cooperative unfolding profile with the midpoint of the unfolding temperature value of \u223c63\u201364\u00b0C, as observed in the unfolding experiment followed by circular dichroism. Our MtSDH structural models and circular dichroism data showed small conformational changes induced by NADP binding. We hope that the data presented here will assist the rational design of antitubercular agents. Proteins 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.21953","type":"journal-article","created":{"date-parts":[[2008,2,7]],"date-time":"2008-02-07T18:21:40Z","timestamp":1202408500000},"page":"720-730","source":"Crossref","is-referenced-by-count":19,"title":["Structural studies of shikimate 5\u2010dehydrogenase from <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1002","volume":"72","author":[{"given":"Helen A.","family":"Arcuri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00falio C.","family":"Borges","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel O.","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 H.","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Ruggiero","family":"Neto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz A.","family":"Basso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di\u00f3genes S.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Walter F.","family":"de Azevedo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,2,7]]},"reference":[{"key":"e_1_2_6_2_2","volume-title":"WHO report, WHO\/CDS\/TB\/2004.331","author":"WHO","year":"2004"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612043383223"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68384-0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1126\/science.257.5073.1055","article-title":"Tuberculosis: commentary on a reemergent killer","volume":"257","author":"Bloom BR","year":"1998","journal-title":"Science"},{"key":"e_1_2_6_6_2","first-page":"301","article-title":"Emergence of Mycobacterium tuberculosis with extensive resistance to second\u2010line drugs\u2014worldwide, 2000\u20132004","volume":"55","author":"CDC (Centers for Disease Control and Prevention)","year":"2006","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040050"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.2.403"},{"key":"e_1_2_6_9_2","first-page":"97","volume-title":"Herbicides and plant metabolism","author":"Coggins JR","year":"1989"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.3109\/10409239009090615"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/338004"},{"key":"e_1_2_6_12_2","volume-title":"Shikimic acid: metabolism and metabolites","author":"Haslam E","year":"1993"},{"key":"e_1_2_6_13_2","first-page":"185","volume-title":"The biology of the Mycobacteria","author":"Ratledge C","year":"1982"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-10-3069"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300794200"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(03)00159-X"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.185.14.4144-4151.2003"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05469.x"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-5928(02)00509-0"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2005.10.004"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2006.11.015"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560041120"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/5.3.191"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2006.05.008"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.14.2994"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945007780058960"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945007780059004"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.22.4673"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg430"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0134(20000815)40:3<502::AID-PROT170>3.0.CO;2-Q"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/9.6.493"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1626"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560030923"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340230306"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0958-1669(95)80074-3"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540040211"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1107\/S002188980502474X"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(85)90134-2"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.10.192"},{"key":"e_1_2_6_42_2","unstructured":"LaskowskiRA MacArthurMW SmithDK JonesDT HutchinsonEG MorrisAL NaylorD MossDS ThorntonJM.PROCHECK v. 3.0\u2014program to check the stereochemistry quality of protein structures\u2014operating instructions.1994."},{"key":"e_1_2_6_43_2","volume-title":"X\u2010PLOR Version 3.1: a system for crystallography and NMR","author":"Br\u00fcnger AT","year":"1992"},{"key":"e_1_2_6_44_2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1107\/S0907444994003112","article-title":"The CCP4 suite: programs for proteins crystallography","volume":"50","author":"Collaborative Computational Project No. 4","year":"1994","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1090-7807(02)00014-9"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1853201"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/356083a0"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360221211"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(00)76630-6"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2005.38.5.624"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(03)00165-5"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.13"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.arplant.50.1.473"}],"container-title":["Proteins: Structure, Function, and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprot.21953","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prot.21953","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T19:23:57Z","timestamp":1696879437000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prot.21953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,7]]},"references-count":52,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,8]]}},"alternative-id":["10.1002\/prot.21953"],"URL":"https:\/\/doi.org\/10.1002\/prot.21953","archive":["Portico"],"relation":{},"ISSN":["0887-3585","1097-0134"],"issn-type":[{"value":"0887-3585","type":"print"},{"value":"1097-0134","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,7]]}}}