TAILIEUCHUNG - Báo cáo khoa học: Structure and function of human a-lactalbumin made lethal to tumor cells (HAMLET)-type complexes

Humana-lactalbumin made lethal to tumor cells (HAMLET) and equine lysozyme with oleic acid (ELOA) are complexes consisting of protein and fatty acid that exhibit cytotoxic activities, drastically differing from the activity of their respective proteinaceous compounds. Since the discovery of HAMLET in the 1990s, a wealth of information has been accumulated, illuminating the structural, functional and therapeutic properties of protein complexes with oleic acid, which is summarized in this review. | MINIREVIEW Structure and function of human a-lactalbumin made lethal to tumor cells HAMLET -type complexes Ann-Kristin Mossberg1 Kenneth Hun Mok1 2 Ludmilla A. Morozova-Roche3 and Catharina Svanborg1 4 1 Department of Microbiology Immunology and Glycobiology MIG Institute of Laboratory Medicine Lund University Sweden 2 Schoolof Biochemistry and Immunology Trinity College Dublin Ireland 3 Department of MedicalBiochemistry and Biophysics Umea University Sweden 4 Singapore Immunology Network SIgN A STAR Singapore Keywords a-lactalbumin cancer cell death ELOA HAMLET lysozyme oleate oleic acid protein folding Correspondence . Mossberg Department of Microbiology Immunology and Glycobiology MIG Institute of Laboratory Medicine Lund University Solvegatan 23 S-223 62 Lund Sweden Fax 46 46 13 74 68 Tel 46 46 222 71 85 E-mail Received 30 April 2010 revised 18 August 2010 accepted 2 September 2010 doi Human a-lactalbumin made lethal to tumor cells HAMLET and equine lysozyme with oleic acid ELOA are complexes consisting of protein and fatty acid that exhibit cytotoxic activities drastically differing from the activity of their respective proteinaceous compounds. Since the discovery of HAMLET in the 1990s a wealth of information has been accumulated illuminating the structural functional and therapeutic properties of protein complexes with oleic acid which is summarized in this review. In vitro both HAMLET and ELOA are produced by using ion-exchange columns preconditioned with oleic acid. However the complex of human a-lactalbu-min with oleic acid with the antitumor activity of HAMLET was found to be naturally present in the acidic fraction of human milk where it was discovered by serendipity. Structural studies have shown that a-lactalbumin in HAMLET and lysozyme in ELOA are partially unfolded molten-globule -like thereby rendering the complexes dynamic and in conformational exchange. HAMLET exists in the monomeric .

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