{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:01:02Z","timestamp":1777525262433,"version":"3.51.4"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Enzymes are complex catalytic machines, which perform sequences of elementary chemical transformations resulting in biochemical function. The building blocks of enzymes, elementary functional loops (EFLs), possess distinct functional signatures and provide catalytic and binding amino acids to the enzyme's active sites. The goal of this work is to obtain primordial prototypes of EFLs that existed before the formation of enzymatic domains and served as their building blocks.<\/jats:p>\n               <jats:p>Results: We developed a computational strategy for reconstructing ancient prototypes of EFLs based on the comparison of sequence segments on the proteomic scale, which goes beyond detection of conserved functional motifs in homologous proteins. We illustrate the procedure by a CxxC-containing prototype with a very basic and ancient elementary function of metal\/metal-containing cofactor binding and redox activity. Acquiring the prototypes of EFLs is necessary for revealing how the original set of protein folds with enzymatic functions emerged in predomain evolution.<\/jats:p>\n               <jats:p>Supplementary Information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <jats:p>Contact: \u00a0igor.berezovsky@uni.no<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr396","type":"journal-article","created":{"date-parts":[[2011,7,4]],"date-time":"2011-07-04T04:22:20Z","timestamp":1309753340000},"page":"2368-2375","source":"Crossref","is-referenced-by-count":20,"title":["Computational reconstruction of primordial prototypes of elementary functional loops in modern proteins"],"prefix":"10.1093","volume":"27","author":[{"given":"Alexander","family":"Goncearenco","sequence":"first","affiliation":[{"name":"1 Computational Biology Unit, Uni Research and 2 Department of Informatics, University of Bergen, N-5008 Bergen, Norway"},{"name":"1 Computational Biology Unit, Uni Research and 2 Department of Informatics, University of Bergen, N-5008 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor N.","family":"Berezovsky","sequence":"additional","affiliation":[{"name":"1 Computational Biology Unit, Uni Research and 2 Department of Informatics, University of Bergen, N-5008 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,6,30]]},"reference":[{"key":"2023012511531681200_B1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. 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