6ip9
Crystal Structure of Lanthanum ion (La3+) bound bovine alpha-lactalbuminCrystal Structure of Lanthanum ion (La3+) bound bovine alpha-lactalbumin
Structural highlights
Function[LALBA_BOVIN] Regulatory subunit of lactose synthase, changes the substrate specificity of galactosyltransferase in the mammary gland making glucose a good acceptor substrate for this enzyme. This enables LS to synthesize lactose, the major carbohydrate component of milk. In other tissues, galactosyltransferase transfers galactose onto the N-acetylglucosamine of the oligosaccharide chains in glycoproteins. Publication Abstract from PubMedCancer remains one of the biggest threats to human society. There are massive demands for compounds to selectively kill cancerous cells. Earlier studies have shown that bovine alpha -lactalbumin made lethal to tumor cells (BAMLET) becomes cytotoxic against cancer cells in complex with oleic acid {Hoque, M. et. al., PLoSOne 8, e68390 (2013)}. In our study, we obtained bovine alpha-lactalbumin complexed with lanthanum ion (La(3+)-B-alpha-LA) and determined its high resolution crystal structure. The natural calcium binding site of bovine alpha-lactalbumin is replaced by lanthanum. The La(3+) complex formation by B-alpha-apo-LA was also supported by various biophysical methods. Interestingly, our complex, La(3+)-B-alpha-LA exhibits much greater anticancer activity against breast cancer cells as compared to the reported BAMLET-oleic acid complex. This study shows that La(3+)-B-alpha-LA complex is preferentially more toxic to MCF-7 cells as compared to KB (oral cancer) and HeLa (cervical) cells, while almost non-toxic to the healthy cells that we studied. Our data indicates that the cytotoxicity of La(3+)-B-alpha-LA against cancer cells is through apoptotic path way. The higher anticancer activity of La(3+)-B-alpha-LA is attributable to the requisite structural changes induced in the protein by La(3+) binding as supported by the crystal structure of the complex. Cytotoxicity of apo bovine alpha-lactalbumin complexed with La(3+) on cancer cells supported by its high resolution crystal structure.,Yarramala DS, Prakash P, Ranade DS, Doshi S, Kulkarni PP, Bhaumik P, Rao CP Sci Rep. 2019 Feb 11;9(1):1780. doi: 10.1038/s41598-018-38024-1. PMID:30741951[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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