Alpha-lactalbumin

Lactalbumin, alpha-, also known as LALBA, is a is_associated_with::protein that in humans is encoded by the LALBA is_associated_with::gene.

Function
α-Lactalbumin is a protein present in the milk of almost all is_associated_with::mammalian species. In primates, alpha-lactalbumin expression is upregulated in response to the hormone is_associated_with::prolactin and increases the production of is_associated_with::lactose.

α-Lactalbumin forms the regulatory subunit of the is_associated_with::lactose synthase (LS) heterodimer and β-1,4-galactosyltransferase (beta4Gal-T1) forms the catalytic component. Together, these proteins enable LS to produce is_associated_with::lactose by transferring is_associated_with::galactose moieties to is_associated_with::glucose. As a multimer, alpha-lactalbumin strongly binds calcium and zinc ions and may possess bactericidal or antitumor activity. A folding variant of human alpha-lactalbumin that may form in acidic environments such as the stomach, called HAMLET, probably induces is_associated_with::apoptosis in tumor and immature cells. The corresponding folding dynamics of alpha-lactalbumin is thus highly unusual.

When formed into a complex with Gal-T1, a is_associated_with::galactosyltransferase, α-lactalbumin, enhances the enzyme's affinity for is_associated_with::glucose by about 1000 times, and inhibits the ability to polymerise multiple is_associated_with::galactose units. This gives rise to a pathway for forming is_associated_with::lactose by converting Gal-TI to is_associated_with::Lactose synthase.

Physical properties
The structure of alpha-lactalbumin is well known and is composed of 123 amino acids and 4 disulfide bridges. The molecular weight is 14178 Da, and the is_associated_with::isoelectric point is between 4.2 and 4.5. One of the main structural differences with is_associated_with::beta-lactoglobulin is that it does not have any free is_associated_with::thiol group that can serve as the starting-point for a covalent aggregation reaction. As a result, pure α-lactalbumin will not form gels upon denaturation and acidification.

Evolution
The sequence comparison of α-lactalbumin shows a strong similarity to that of is_associated_with::lysozymes, specifically the Ca2+-binding c-lysozyme. So the expected evolutionary history is that gene duplication of the c-lysozyme was followed by mutation. This gene predates the last common ancestor of mammals and birds, which probably puts its origin at about 300 Ma.