Proton pump inhibitors, such as omeprazole, pantoprazole and lansoprazole, are an important group of clinically used drugs. Generally, they are considered safe without direct toxicity. Nevertheless, their long-term use can be associated with a higher risk of some serious pathological states (e.g. amnesia and oncological and neurodegenerative states). It is well known that dysregulation of the metabolism of transition metals (especially iron ions) plays a significant role in these pathological states and that the above drugs can form complexes with metal ions. However, to the best of our knowledge, this phenomenon has not yet been described in water systems. Therefore, we studied the interaction between these drugs and transition metal ions in the surrounding water environment (water/DMSO, 99:1, v/v) by absorption spectroscopy. In the presence of Fe(III), a strong redshift was observed, and more importantly, the affinities of the drugs (represented as binding constants) were strong enough, especially in the case of omeprazole, so that the formation of a metallocomplex cannot be excluded during the explanation of their side effects.

• MeSH
• inhibitory protonové pumpy chemie   MeSH
• komplexní sloučeniny chemie   MeSH
• lanzoprazol * chemie   MeSH
• omeprazol chemie   MeSH
• pantoprazol chemie   MeSH
• přechodné kovy chemie   MeSH
• spektrofotometrie * MeSH
• voda chemie   MeSH
• železité sloučeniny chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Staphylococcus aureus uses IsdG and IsdI to convert heme into a mixture of staphylobilin isomers, 15-oxo-β-bilirubin and 5-oxo-δ-bilirubin, formaldehyde, and iron. The highly ruffled heme found in the heme-IsdI and IsdG complexes has been proposed to be responsible for the unique heme degradation products. We employed resonance Raman (RR) and electron paramagnetic resonance (EPR) spectroscopies to examine the coordination and electronic structures of heme bound to IsdG and IsdI. Heme complexed to IsdG and IsdI is coordinated by a neutral histidine. The trans ligand is hydroxide in the ferric alkaline form of both proteins. In the ferric neutral form at pH 6.0, heme is six-coordinated with water as the sixth ligand for IsdG and is in the mixture of the five-coordinated and six-coordinated species for IsdI. In the ferrous CO-bound form, CO is strongly hydrogen bonded with a distal residue. The marker lines, ν2 and ν3, appear at frequencies that are distinct from other proteins having planar hemes. The EPR spectra for the ferric hydroxide and cyanide states might be explained by assuming the thermal mixing of the d-electron configurations, (dxy)2(dxz,dyz)3 and (dxz,dyz)4(dxy)1. The fraction for the latter becomes larger for the ferric cyanide form. In the ferric neutral state at pH 6.0, the quantum mechanical mixing of the high and intermediate spin configurations might explain the peculiar frequencies of ν2 and ν3 in the RR spectra. The heme ruffling imposed by IsdG and IsdI gives rise to unique electronic structures of heme, which are expected to modulate the first and subsequent steps of the heme oxygenation.

• MeSH
• bakteriální proteiny chemie   MeSH
• elektronová paramagnetická rezonance MeSH
• hem chemie   MeSH
• lidé MeSH
• oxid uhelnatý chemie   MeSH
• oxygenasy se smíšenou funkcí chemie   MeSH
• oxygenasy chemie   MeSH
• Ramanova spektroskopie MeSH
• stafylokokové infekce mikrobiologie   MeSH
• Staphylococcus aureus chemie   MeSH
• vodíková vazba MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH