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X-ray structure of lysozyme obtained upon reaction with [VIVO(empp)2] (Structure A)X-ray structure of lysozyme obtained upon reaction with [VIVO(empp)2] (Structure A)
Structural highlights
FunctionLYSC_CHICK Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.[1] Publication Abstract from PubMedVanadium 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 [V(IV)O(empp)(2)] (where Hempp is 1-methyl-2-ethyl-3-hydroxy-4(1H)-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 [V(IV)O(empp)(2)] and [V(IV)O(empp)(H(2)O)](+), 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 [V(IV)O(empp)(H(2)O)](+) to the side chain of Asp48, and noncovalent binding of cis-[V(IV)O(empp)(2)(H(2)O)], [V(IV)O(empp)(H(2)O)](+), [V(IV)O(empp)(H(2)O)(2)](+), and of an unusual trinuclear oxidovanadium(V) complex, [V(V)(3)O(6)(empp)(3)(H(2)O)], 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. Implications of Protein Interaction in the Speciation of Potential V(IV)O-Pyridinone Drugs.,Ferraro G, Paolillo M, Sciortino G, Pisanu F, Garribba E, Merlino A Inorg Chem. 2023 May 29;62(21):8407-8417. doi: 10.1021/acs.inorgchem.3c01041. , Epub 2023 May 17. PMID:37195003[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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