{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T15:55:29Z","timestamp":1746806129866,"version":"3.40.5"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2011,11,29]],"date-time":"2011-11-29T00:00:00Z","timestamp":1322524800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"Ministry of University and Research of Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ISRN Hematology"],"published-print":{"date-parts":[[2011,11,29]]},"abstract":"We report the first case of cosegregation of two haemoglobins (Hbs): HbG-Philadelphia [\u03b1<\/mml:mi>68(E17)<\/mml:mtext>Asn<\/mml:mtext>\u2192<\/mml:mo>Lys<\/mml:mtext><\/mml:mrow><\/mml:math>] and HbDuarte [\u03b2<\/mml:mi>62(E6)<\/mml:mtext>Ala<\/mml:mtext>\u2192<\/mml:mo>Pro<\/mml:mtext><\/mml:mrow><\/mml:math>]. The proband is a young patient heterozygous also for\u03b2<\/mml:mi>\u2218<\/mml:mo><\/mml:msup><\/mml:math>-thalassaemia. We detected exclusively two haemoglobin variants: HbDuarte and HbG-Philadelphia\/Duarte. Functional study of the new double variant HbG-Philadelphia\/Duarte exhibited an increase in oxygen affinity, with a slight decrease of cooperativity and Bohr effect. This functional behaviour is attributed to\u03b2<\/mml:mi>62<\/mml:mo>Ala<\/mml:mtext>\u2192<\/mml:mo>Pro<\/mml:mtext><\/mml:mrow><\/mml:math>instead of\u03b1<\/mml:mi>68<\/mml:mo>Asn<\/mml:mtext>\u2192<\/mml:mo>Lys<\/mml:mtext><\/mml:mrow><\/mml:math>substitution. Indeed, HbG-Philadelphia isolated in our laboratory from blood cells donor carrier for this variant is not affected by any functional modification, whereas purified Hb Duarte showed functional properties very similar to the double variant. NMR and MD simulation studies confirmed that the presence of Pro instead of Ala at the\u03b2<\/mml:mi>62<\/mml:mo><\/mml:math>position produces displacement of the E helix and modifications of the tertiary structure. The substitution\u03b1<\/mml:mi>68(E17)<\/mml:mtext>Asn<\/mml:mtext>\u2192<\/mml:mo>Lys<\/mml:mtext><\/mml:mrow><\/mml:math>does not cause significant structural and dynamical modifications of the protein. A possible structure-based rational of substitution effects is suggested.<\/jats:p>","DOI":"10.5402\/2011\/735314","type":"journal-article","created":{"date-parts":[[2010,11,30]],"date-time":"2010-11-30T10:24:52Z","timestamp":1291112692000},"page":"1-10","source":"Crossref","is-referenced-by-count":1,"title":["Structural and Functional Characterization of a New Double Variant Haemoglobin (HbG-Philadelphia\/Duarte\u03b1<\/mml:mi>2<\/mml:mn>68<\/mml:mn>Asn<\/mml:mtext>\u2192<\/mml:mo>Lys<\/mml:mtext><\/mml:mrow><\/mml:msubsup>\u03b2<\/mml:mi>2<\/mml:mn>62<\/mml:mn>Ala<\/mml:mtext>\u2192<\/mml:mo>Pro<\/mml:mtext><\/mml:mrow><\/mml:msubsup><\/mml:mrow><\/mml:math>)"],"prefix":"10.5402","volume":"2011","author":[{"given":"Antonella","family":"Fais","sequence":"first","affiliation":[{"name":"Department of Sciences Applied to Biosystems, University of Cagliari, S.P. Monserrato-Sestu km 0.700, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariano","family":"Casu","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Cagliari, S.P. Monserrato-Sestu km 0.700, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Ruggerone","sequence":"additional","affiliation":[{"name":"SLACS, Istituto Officina dei Materiali del CNR and Department of Physics, University of Cagliari, S.P. Monserrato-Sestu km 0.700, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"SLACS, Istituto Officina dei Materiali del CNR and Department of Physics, University of Cagliari, S.P. Monserrato-Sestu km 0.700, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Porcu","sequence":"additional","affiliation":[{"name":"Department of Sciences Applied to Biosystems, University of Cagliari, S.P. Monserrato-Sestu km 0.700, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Era","sequence":"additional","affiliation":[{"name":"Department of Sciences Applied to Biosystems, University of Cagliari, S.P. Monserrato-Sestu km 0.700, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Anedda","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Cagliari, S.P. Monserrato-Sestu km 0.700, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Carla","family":"Sollaino","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotecnologies Sciences, University of Cagliari, via Jenner, 09121 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renzo","family":"Galanello","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotecnologies Sciences, University of Cagliari, via Jenner, 09121 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Corda","sequence":"additional","affiliation":[{"name":"Department of Sciences Applied to Biosystems, University of Cagliari, S.P. 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