9H49

Crystal structure of the adduct between human serum transferrin (apo-form) and cisplatin

9H49 の概要

• エントリーDOI: 10.2210/pdb9h49/pdb
• 分子名称: Serotransferrin, CITRIC ACID, PLATINUM (II) ION, ... (5 entities in total)
• 機能のキーワード: cisplatin, metallodrug, anticancer, metal complex, methionine/cisplatin adduct, metal transport
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 152638.26

構造登録者

Troisi, R.,Galardo, F.,Ferraro, G.,Sica, F.,Merlino, A. (登録日: 2024-10-17, 公開日: 2025-01-22, 最終更新日: 2025-01-29)

主引用文献

Troisi, R.,Galardo, F.,Ferraro, G.,Lucignano, R.,Picone, D.,Marano, A.,Trifuoggi, M.,Sica, F.,Merlino, A.
Cisplatin/Apo-Transferrin Adduct: X-ray Structure and Binding to the Transferrin Receptor 1.
Inorg.Chem., 64:761-765, 2025

PubMed Abstract: Here, we report the X-ray structure of the adduct formed upon reaction of cisplatin, one of the most prescribed anticancer agents for the clinic treatment of solid tumors, with the apo-form of human serum transferrin (hTF). Two Pt binding sites were identified in both molecules of the adduct present in the crystal asymmetric unit: Pt binds close to the side chains of Met256 and Met499 at the N- and C-lobe, respectively. In the crystal structure, the cisplatin moiety bound to Met256 also interacts with Ser616 from a symmetry related molecule. Structural analyses, together with in solution data, demonstrate that the presence of iron does not affect the ability of hTF to bind cisplatin and that the cisplatin binding does not significantly alter the overall conformation of the different forms of the protein that remain able to form a complex with the transferrin receptor 1 (TfR1). These data suggest that the different hTF forms can be used as nanocarriers for targeted (combined) metallodrug delivery.

PubMed: 39711171
DOI: 10.1021/acs.inorgchem.4c04435

実験手法

X-RAY DIFFRACTION (3.52 Å)