9rzr | pdb_00009rzr
Hen Egg-White Lysozyme (HEWL) complexed with a Lindqvist-type hexavanadate (V6-Hex) polyoxometalate
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 PubMedMolecular metal-oxo nanoclusters with tunable redox and structural properties have emerged as powerful bio-inorganic tools in catalysis, protein crystallization, and therapeutic applications. Despite their potential, interactions between discrete clusters and proteins are predominantly driven by nonspecific intermolecular interactions, which limit precise control over binding sites and functional outcomes. In this work, we introduce a new strategy to achieve site-directed binding of vanadium-based polyoxometalate clusters (POVs) to distinct regions of Hen Egg White Lysozyme (HEWL), an archetypal antimicrobial enzyme. Three novel hybrid POVs were designed and fully characterized, starting from an azide-functionalized cluster (Na-V(6)-N(3)), which was subsequently post-functionalized with a hydrophobic hexyne group (Na-V(6)-Hex) to probe nonpolar interactions, and alpha-d-mannopyranoside (Na-V(6)-Man) to mimic the protein's natural substrate. Structural and spectroscopic analyses demonstrated that, in contrast to conventional nonhybrid POV clusters which bind nonspecifically to peripheral positively charged protein patches, the hybrid POVs achieve distinct binding behaviors. Specifically, Na-V(6)-N(3) and Na-V(6)-Man selectively target the glycosidic pocket, resembling the binding of the protein's natural substrate, while Na-V(6)-Hex exhibits an unprecedented crystallization of two POV clusters in close proximity, which wrap around the protein surface. These findings highlight that strategic organic functionalization can circumvent electrostatic barriers to achieve site-selective cluster-protein interactions, thus opening new avenues for the application of metal-oxo clusters in biotechnology, drug delivery, and medicine. Finding the Key: Binding of Metal-Oxo Clusters to the Enzyme Active Site Enabled by "Click" (Bio)Conjugation.,Kalandia G, Declerck K, Salazar Marcano DE, Gourmand R, Moussawi MA, Parac-Vogt TN Angew Chem Int Ed Engl. 2025 Sep 23:e202518349. doi: 10.1002/anie.202518349. PMID:40985763[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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