Sandbox 43: Difference between revisions
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== '''Metal Ions associated with α-lactalbumin'''== | == '''Metal Ions associated with α-lactalbumin'''== | ||
α-lactalbumin is a small protein with calcium ions as cofactors. The binding of the calcium ion increases the stability of the protein in its native conformation and makes the folding of the protein much faster. The binding of the calcium ion acts of a nucleus for the stabilization of the tertiary structure in the protein, without it the process is much slower.<ref>Natalia A. Bushmarina, Clement E. Blanchet, Gregory Vernier, and Vincent Forge. 2006. Cofactor effects on the protein folding reaction: Acceleration of a-lactalbumin refolding by metal ions ''Protein Science'' 15:659–671</ref> In α-lactalbumin native conformation the calcium ion is bound to a unique binding loop.<ref name="ii"> </ref> The calcium binding site is located in the β-domain and is formed by three Asp side chains and two mainchain carbonyls. This site the calcium ion has a pentagonal bypyramidal coordination.<ref name="iv"> </ref> <ref name="iii"> </ref> A secondary calcium binding site involves the residues Thr, Gln, Leu, and Asp. In this site the calcium ion has a tetrahedral coordination.<ref name="iv"> Protein Data Bank. 2009. European Bioinformatics Institute. <http://www.ebi.ac.uk/thornton-srv/databases/pdbsum/> Retrieved Sept.19,2009.</ref> The <scene name='Sandbox_43/Cal_res/1'>residues</scene> that come into contact with the calcium ion are shown to the right. Protection from thermal, guanidine HCL and urea denaturation is provided by the stability given to the protein from the calcium ion binding. The calcium-binding site has also been shown to weakly bind Mg2+, Na2+, and K+ also. Removal of the calcium ion has shown to induce a conformational change. In the presence of denaturants or absence of calcium ions α-lactalbumin adopts the molten globule state and characterized by the conserved secondary structure but fluctuating tertiary structure.<ref name="ii"> </ref> α-lactalbumin, in its native state, possesses a relatively strong Zn2+ site causing subtle changes in α-lactalbumin structure upon binding to the calcium loaded protein. The Zn2+ is important in the binding of glucose in the lactose synthase complex.<ref name="ii"> </ref> | α-lactalbumin is a small protein with calcium ions as cofactors. The binding of the calcium ion increases the stability of the protein in its native conformation and makes the folding of the protein much faster. The binding of the calcium ion acts of a nucleus for the stabilization of the tertiary structure in the protein, without it the process is much slower.<ref>Natalia A. Bushmarina, Clement E. Blanchet, Gregory Vernier, and Vincent Forge. 2006. Cofactor effects on the protein folding reaction: Acceleration of a-lactalbumin refolding by metal ions ''Protein Science'' 15:659–671</ref> In α-lactalbumin native conformation the calcium ion is bound to a unique binding loop.<ref name="ii"> </ref> The calcium binding site is located in the β-domain and is formed by three Asp side chains and two mainchain carbonyls. This site the calcium ion has a pentagonal bypyramidal coordination.<ref name="iv"> </ref> <ref name="iii"> </ref> A secondary calcium binding site involves the residues Thr, Gln, Leu, and Asp. In this site the calcium ion has a tetrahedral coordination.<ref name="iv"> Protein Data Bank. 2009. European Bioinformatics Institute. <http://www.ebi.ac.uk/thornton-srv/databases/pdbsum/> Retrieved Sept.19,2009.</ref> The <scene name='Sandbox_43/Cal_res/1'>residues</scene> that come into contact with the calcium ion are shown to the right. Protection from thermal, guanidine HCL and urea denaturation is provided by the stability given to the protein from the calcium ion binding. The calcium-binding site has also been shown to weakly bind Mg2+, Na2+, and K+ also. Removal of the calcium ion has shown to induce a conformational change. In the presence of denaturants or absence of calcium ions α-lactalbumin adopts the molten globule state and characterized by the conserved secondary structure but fluctuating tertiary structure.<ref name="ii"> </ref> α-lactalbumin, in its native state, possesses a relatively strong Zn2+ site causing subtle changes in α-lactalbumin structure upon binding to the calcium loaded protein. The Zn2+ is important in the binding of glucose in the lactose synthase complex.<ref name="ii"> </ref> | ||
=='''Research'''== | |||
HAMLET (human a-lactalbumin made lethal to tumor cells) is made up of partially unfolded α-lactalbumin and oleic acid. HAMLET has been shown to kill a wide range of tumor cells and embryonal cells but not healthy differentiated cells. It is thought that HAMLET initiate macroautophagy in tumor cells. HAMLET was shown to affect the mitochondria and to cause an apoptotic response with Cytochrome c release, low capase activation, phosphatidylserine exposure and DNA fragmentation.<ref>Sonja Aits, Lotta Gustafsson, Oskar Hallgren, Patrick Brest, Mattias Gustafsson, Maria Trulsson, Ann-Kristin Mossberg, Hans-Uwe Simon, Baharia Mograbi and Catharina Svanborg. 2009. HAMLET (human a-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death. ''Int. J. Cancer'' 124, 1008–1019</ref> | |||
==References== | ==References== | ||
{{Reflist}} | {{Reflist}} | ||
