TY - JOUR
T1 - Protein-Protein Stabilization in VIVO/8-Hydroxyquinoline–Lysozyme Adducts
AU - Paolillo, Maddalena
AU - Ferraro, Giarita
AU - Pisanu, Federico
AU - Maréchal, Jean Didier
AU - Sciortino, Giuseppe
AU - Garribba, Eugenio
AU - Merlino, Antonello
N1 - Publisher Copyright:
© 2024 Wiley-VCH GmbH.
PY - 2024/10/1
Y1 - 2024/10/1
N2 - The binding of the potential drug [VIVO(8-HQ)2], where 8-HQ is 8-hydroxyquinolinato, with hen egg white lysozyme (HEWL) was evaluated through spectroscopic (electron paramagnetic resonance, EPR, and UV-visible), spectrometric (electrospray ionization-mass spectrometry, ESI-MS), crystallographic (X-ray diffraction, XRD), and computational (DFT and docking) studies. ESI-MS indicates the interaction of [VIVO(8-HQ)(H2O)]+ and [VIVO(8-HQ)2(H2O)] species with HEWL. Room temperature EPR spectra suggest both covalent and non-covalent binding of the two different V-containing fragments. XRD analyses confirm these findings, showing that [VIVO(8-HQ)(H2O)]+ interacts covalently with the solvent exposed Asp119, while cis-[VIVO(8-HQ)2(H2O)] non-covalently with Arg128 and Lys96 from a symmetry mate. The covalent binding of [VIVO(8-HQ)(H2O)]+ to Asp119 is favored by a π-π contact with Trp62 and a H-bond with Asn103 of a symmetry-related molecule. Additionally, the covalent binding of VVO2+ to Asp48 and non-covalent binding of other V-containing fragments to Arg5, Cys6, and Glu7 are revealed. Molecular docking indicates that, in the absence of the interactions occurring at the protein-protein interface close to Asp119, the covalent binding to Glu35 or Asp52 should be preferred. Such a protein-protein stabilization could be more common than what believed up today, at least in the solid state, and should be considered in the characterization of metal-protein adducts.
AB - The binding of the potential drug [VIVO(8-HQ)2], where 8-HQ is 8-hydroxyquinolinato, with hen egg white lysozyme (HEWL) was evaluated through spectroscopic (electron paramagnetic resonance, EPR, and UV-visible), spectrometric (electrospray ionization-mass spectrometry, ESI-MS), crystallographic (X-ray diffraction, XRD), and computational (DFT and docking) studies. ESI-MS indicates the interaction of [VIVO(8-HQ)(H2O)]+ and [VIVO(8-HQ)2(H2O)] species with HEWL. Room temperature EPR spectra suggest both covalent and non-covalent binding of the two different V-containing fragments. XRD analyses confirm these findings, showing that [VIVO(8-HQ)(H2O)]+ interacts covalently with the solvent exposed Asp119, while cis-[VIVO(8-HQ)2(H2O)] non-covalently with Arg128 and Lys96 from a symmetry mate. The covalent binding of [VIVO(8-HQ)(H2O)]+ to Asp119 is favored by a π-π contact with Trp62 and a H-bond with Asn103 of a symmetry-related molecule. Additionally, the covalent binding of VVO2+ to Asp48 and non-covalent binding of other V-containing fragments to Arg5, Cys6, and Glu7 are revealed. Molecular docking indicates that, in the absence of the interactions occurring at the protein-protein interface close to Asp119, the covalent binding to Glu35 or Asp52 should be preferred. Such a protein-protein stabilization could be more common than what believed up today, at least in the solid state, and should be considered in the characterization of metal-protein adducts.
KW - computational calculations
KW - ESI-MS spectrometry
KW - V-based drugs
KW - V-protein adducts
KW - X-ray crystallography
KW - Electron Spin Resonance Spectroscopy
KW - Crystallography, X-Ray
KW - Oxyquinoline/chemistry
KW - Animals
KW - Spectrometry, Mass, Electrospray Ionization
KW - Hydrogen Bonding
KW - Chickens
KW - Protein Binding
KW - Molecular Docking Simulation
KW - Protein Stability
KW - Binding Sites
KW - Muramidase/chemistry
UR - http://www.scopus.com/inward/record.url?scp=85205387775&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/18d33fc3-756c-3411-a496-60ac570f26ec/
U2 - 10.1002/chem.202401712
DO - 10.1002/chem.202401712
M3 - Article
C2 - 38923243
AN - SCOPUS:85205387775
SN - 0947-6539
VL - 30
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 55
M1 - e202401712
ER -