Sandbox 81
From Proteopedia
Contents |
Alpha Lactalbumin
α-lactalbumin is a major protein in all kinds of milk studied so far. [1] α- lactalbumin contributes to cell lytic activity, cell growth inhibition, and apoptosis but most importantly, it interacts with UDP-galactosyltransferase [1] to form lactose synthetase via the following reaction:
UDP-galactose + glucose -+ lactose + UDP [2]
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| 1a4v, resolution 1.80Å () | |||||||||
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| Ligands: | |||||||||
| Activity: | Lactose synthase, with EC number 2.4.1.22 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Structure
α-lactalbumin is a small globular protein, with 123 residues [3], stabilized by four disulfide bonds with two structural domains. One domain is rich in α-helices, the other is rich in β-sheets and has a calcium binding site. [4]
The has nine alpha helices shown as pink rockets, and two beta strands shown as yellow planks.[3]
: with nonpolar side chains in gray, polar side chains in purple, and associated water molecules in red.
: calcium ligands with amino acid contacts. water in pink, oxygen in red.
:cations in blue, anions in red, hydrophobic in gray, polar uncharged in light purple, backbone in dark purple.
Function
Recent Studies
Tryptophan is a component of many alpha-lactalbumin proteins [5], the availability of which changes the ratio of plasma tryptophan to the sum of larger neutral amino acids (Trp-LNAA ratio). Tryptophan is a serotonin precursor and proper serotonin function in the brain has been shown to promote sleep regulation and cognitive processes. [6] Deficient serotonin function, possibly from chronic stress [5], can result in difficulty sleeping and therefore behavioral decline. Recent studies have shown that consumption of alpha-lactalbumin protein with enriched tryptophan content caused increased alertness and performance the morning after [6].
Many studies have found that infants who are formula- fed have different growth and amino acid patterns from breast-fed infants from the lack of alpha-lactalbumin. The addition of bovine alpha-lactalbumin to formula makes the growth and plasma amino acid patterns of formula-fed infants more similar to those of breast-fed infants, and improves their growth.[7] HAMLET (human alpha-lactalbumin made lethal to tumor cells) is the topic of much recent study. Alpha-lactalbumin is converted into a folding variant with altered biological function which can induce apoptosis in tumor and premature cells, healthy cells are resistant to this. For HAMLET to form partial unfolding needs to occur, as well as the presence of C18:1, a fatty acid. The studies have shown that HAMLET may help lower cancer in breast-fed infants by killing the tumor cells in their stomachs because the low pH releases Ca21 from the binding site and activates lipases that hydrolyze free fatty acids from milk triglycerides.[8]
References
- ↑ 1.0 1.1 Vilotte JL. Alpha-lactalbumin: Gene Structure and Expression. <http://mammary.nih.gov/Reviews/gene_expression/Vilotte001/index.html>.
- ↑ Fitzgerald DK, Brodbeck URS, Kiyosawa I, Mawal R, Colvin B, Ebner KE. 1970. α-lactalbumin and the Lactose Synthetase Reaction. The Journal of Biological Chemistry. 245(8): 2103-2108.
- ↑ 3.0 3.1 PDBSUM. http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=1a4v&template=protein.html&o=DISULPHIDES&l=1&s=1&c=8&chain=A
- ↑ Hendrix TM, Griko Y, Privalov P. 1996. Energetics of structural domains in α-lactalbumin. Protein Science. 5923-5931.
- ↑ 5.0 5.1 Markus CR, Olivier B, de Haan EH. 2002. Whey protein rich in alpha-lactalbumin increases the ratio of plasma tryptophan to the sum of the other larger neutral amino acids and improves cognitive performance in stress vulnerable subjects. Am J Clin Nutr. 75(6):1051-1056.
- ↑ 6.0 6.1 Markus CR, Jonkman LM, Lammers JH, Deutz NE, Messer MH, Rigtering N. 2005. Evening intake of alpha-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention. Am J Clin Nutr. 81(5):1026-1033.
- ↑ Sandström O, Lönnderdal B, Graverholt G, Hernell O. 2008. Effects of alpha-lactalbumin-enriched formula containing different concentrations of glycomacropeptide on infant nutrition. Am J Clin Nutr. 87(4): 921-928.
- ↑ Svensson M, Hakansson A, Mossberg AK, Linse S, Svanborg C. 2000. Conversion of α-lactalbumin to a protein inducing apoptosis. PNAS. 97(8): 4221-4226.
