{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T07:58:52Z","timestamp":1761292732119},"reference-count":75,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T00:00:00Z","timestamp":1230681600000},"content-version":"vor","delay-in-days":4596,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[1996,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The question of parallel (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrel fold evolution remains unclear, owing mainly to the lack of sequence homology throughout the amino acid sequences of (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrel enzymes. The \u201cclassical\u201d approaches used in the search for homologies among (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrels (e.g., production of structurally based alignments) have yielded alignments perfect from the structural point of view, but the approaches have been unable to reveal the homologies. These are proposed to be \u201chidden\u201d in (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrel enzymes. The term \u201chidden homology\u201d means that the alignment of sequence stretches proposed to be homologous need not be structurally fully satisfactory. This is due to the very long evolutionary history of all (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrels. This work identifies so\u2010called hidden homology around the strand 02 that is flanked by loops containing invariant glycines and prolines in 17 different (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrel enzymes, i.e., roughly in half of all currently known (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrel proteins. The search was based on the idea that a conserved sequence region of an (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrel enzyme should be more or less conserved also in the equivalent part of the structure of the other enzymes with this folding motif, given their mutual evolutionary relatedness. For this purpose, the sequence region around the well\u2010conserved second \u03b2\u2010strand of \u03b1\u2010amylase flanked by the invariant glycine and proline (56_GFTAIWITP, <jats:italic>Aspergillus oryzae \u03b1<\/jats:italic>\u2010amylase numbering), was used as the sequence\u2010structural template. The proposal that the second \u03b2\u2010strand of (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrel fold is important from the evolutionary point of view is strongly supported by the increasing trend of the observed \u03b22\u2010strand structural similarity for the pairs of (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrel enzymes: \u03b1\u2010amylase and the \u03b1\u2010subunit of tryptophan synthase, \u03b1\u2010amylase and mandelate racemase, and \u03b1\u2010amylase and cyclodextrin glycosyltransferase. This trend is also in agreement with the existing evolutionary division of the entire family of (\u03b1\/\u03b2)<jats:sub>8<\/jats:sub>\u2010barrel proteins.<\/jats:p>","DOI":"10.1002\/pro.5560050615","type":"journal-article","created":{"date-parts":[[2010,8,11]],"date-time":"2010-08-11T09:15:45Z","timestamp":1281518145000},"page":"1136-1143","source":"Crossref","is-referenced-by-count":13,"title":["Invariant glycines and prolines flanking in loops the strand \u03b22 of various (\u03b1\/\u03b2)<sub>8<\/sub>\u2010barrel enzymes: A hidden homology?"],"prefix":"10.1002","volume":"5","author":[{"given":"Stefan","family":"Jane\u010dek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,12,31]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/8.12.1189"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/255609a0"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50471-9"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(01)00229-5"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00254a008"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560040213"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0959-440X(91)90094-A"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1107\/S0907444994003112","article-title":"Collaborative Computational Project Number 4. 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