8OM8

X-ray structure of lysozyme obtained upon reaction with [VIVO(empp)2] (Structure A)

これはPDB形式変換不可エントリーです。

8OM8 の概要

• エントリーDOI: 10.2210/pdb8om8/pdb
• 分子名称: Lysozyme C, ACETATE ION, tris-[(1-methyl-2-ethyl-3-hydroxy-4(1H)-pyridinone)]-V(V)3O7, ... (7 entities in total)
• 機能のキーワード: metallodrugs, protein metalation, biologically active v compounds, metal-protein interactions, hydrolase
• 由来する生物種: Gallus gallus (chicken)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15543.45

構造登録者

Paolillo, M.,Ferraro, G.,Merlino, A. (登録日: 2023-03-31, 公開日: 2023-06-07, 最終更新日: 2024-11-13)

主引用文献

Ferraro, G.,Paolillo, M.,Sciortino, G.,Pisanu, F.,Garribba, E.,Merlino, A.
Implications of Protein Interaction in the Speciation of Potential V IV O-Pyridinone Drugs.
Inorg.Chem., 62:8407-8417, 2023

PubMed Abstract: Vanadium complexes (VCs) are promising agents for the treatment, among others, of diabetes and cancer. The development of vanadium-based drugs is mainly limited by a scarce knowledge of the active species in the target organs, which is often determined by the interaction of VCs with biological macromolecules like proteins. Here, we have studied the binding of [VO(empp)] (where Hempp is 1-methyl-2-ethyl-3-hydroxy-4(1)-pyridinone), an antidiabetic and anticancer VC, with the model protein hen egg white lysozyme (HEWL) by electrospray ionization-mass spectrometry (ESI-MS), electron paramagnetic resonance (EPR), and X-ray crystallography. ESI-MS and EPR techniques reveal that, in aqueous solution, both the species [VO(empp)] and [VO(empp)(HO)], derived from the first one upon the loss of a empp(-) ligand, interact with HEWL. Crystallographic data, collected under different experimental conditions, show covalent binding of [VO(empp)(HO)] to the side chain of Asp48, and noncovalent binding of -[VO(empp)(HO)], [VO(empp)(HO)], [VO(empp)(HO)], and of an unusual trinuclear oxidovanadium(V) complex, [VO(empp)(HO)], with accessible sites on the protein surface. The possibility of covalent and noncovalent binding with different strength and of interaction with various sites favor the formation of adducts with the multiple binding of vanadium moieties, allowing the transport in blood and cellular fluids of more than one metal-containing species with a possible amplification of the biological effects.

PubMed: 37195003
DOI: 10.1021/acs.inorgchem.3c01041

実験手法

X-RAY DIFFRACTION (1.08 Å)