6IP9

Crystal Structure of Lanthanum ion (La3+) bound bovine alpha-lactalbumin

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6IP9 の概要

• エントリーDOI: 10.2210/pdb6ip9/pdb
• 分子名称: Alpha-lactalbumin, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: lanthanum, bovine alpha-lactalbumin, hamlet, bamlet, metal binding protein
• 由来する生物種: Bos taurus (Bovine)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14529.11

構造登録者

Prakash, P.,Yarramala, S.D.,Rao, C.P.,Bhaumik, P. (登録日: 2018-11-02, 公開日: 2019-02-20, 最終更新日: 2024-11-06)

主引用文献

Yarramala, D.S.,Prakash, P.,Ranade, D.S.,Doshi, S.,Kulkarni, P.P.,Bhaumik, P.,Rao, C.P.
Cytotoxicity of apo bovine alpha-lactalbumin complexed with La3+on cancer cells supported by its high resolution crystal structure.
Sci Rep, 9:1780-1780, 2019

PubMed Abstract: Cancer 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 α -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 α-lactalbumin complexed with lanthanum ion (La-B-α-LA) and determined its high resolution crystal structure. The natural calcium binding site of bovine α-lactalbumin is replaced by lanthanum. The La complex formation by B-α-apo-LA was also supported by various biophysical methods. Interestingly, our complex, La-B-α-LA exhibits much greater anticancer activity against breast cancer cells as compared to the reported BAMLET-oleic acid complex. This study shows that La-B-α-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-B-α-LA against cancer cells is through apoptotic path way. The higher anticancer activity of La-B-α-LA is attributable to the requisite structural changes induced in the protein by La binding as supported by the crystal structure of the complex.

PubMed: 30741951
DOI: 10.1038/s41598-018-38024-1

実験手法

X-RAY DIFFRACTION (1.85 Å)