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Here, a variety of computational studies were performed to enhance understanding of the structure and function of REX proteins in Trypanosoma<\/jats:italic> and Leishmania<\/jats:italic> species.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Sequence analysis and homology modeling of the Endonuclease\/Exonuclease\/Phosphatase (EEP) domain at the C-terminus of REX1 and REX2 highlights a common active site shared by all EEP domains. Phylogenetic analysis indicates that REX proteins contain a distinct subfamily of EEP domains. Inspection of three-dimensional models of the EEP domain in Trypanosoma brucei<\/jats:italic> REX1 and REX2, and Leishmania major<\/jats:italic> REX1 suggests variations of previously characterized key residues likely to be important in catalysis and determining substrate specificity.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n We have identified features of the REX EEP domain that distinguish it from other family members and hence subfamily specific determinants of catalysis and substrate binding. The results provide specific guidance for experimental investigations about the role(s) of REX proteins in RNA editing.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/1471-2105-7-305","type":"journal-article","created":{"date-parts":[[2006,6,16]],"date-time":"2006-06-16T18:31:18Z","timestamp":1150482678000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Taking U out, with two nucleases?"],"prefix":"10.1186","volume":"7","author":[{"given":"I Saira","family":"Mian","sequence":"first","affiliation":[]},{"given":"Elizabeth A","family":"Worthey","sequence":"additional","affiliation":[]},{"given":"Reza","family":"Salavati","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2006,6,16]]},"reference":[{"key":"1044_CR1","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/S0092-8674(02)00653-0","volume":"108","author":"S Madison-Antenucci","year":"2002","unstructured":"Madison-Antenucci S, Grams J, Hajduk SL: Editing machines: the complexities of trypanosome RNA editing. 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