caa a22 4500 605507627 CHVBK 20210128100633.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00775-015-1301-3 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1301-3 Glutathione-coordinated [2Fe-2S] cluster is stabilized by intramolecular salt bridges [Elektronische Daten] [Jingwei Li, Stephen Pearson, Kevin Fenk, J. Cowan] Halide salts of alkali and alkaline earth metals were used to probe the contributions of intramolecular salt bridge formation on the stability of glutathione-coordinated [2Fe-2S] cluster toward hydrolysis. The effect of ionic strength on cluster stability was quantitatively investigated by application of Debye-Hückel theory to the rates of hydrolysis. Results from this study demonstrate that ionic strength influences the stability of the cluster, with the rate of cluster degradation depending on the charge density, hydrated ionic radius, and hydration energy. The identity of the salt ions was also observed to be correlated with the binding affinity toward the cluster. Based on the modified Debye-Hückel equation and counterion screening effect, these results suggest that interactions between glutathione molecules in the [2Fe-2S](GS)4 cluster is via salt bridges, in agreement with our previous results where modifications of glutathione carboxylates and amines prevented solution aggregation and cluster formation. These results not only provide a rationale for the stability of such clusters under physiological conditions, but also suggest that the formation of glutathione-complexed [2Fe-2S] cluster from a glutathione tetramer may be facilitated by salt bridge interactions between glutathione molecules prior to cluster assembly, in a manner consistent with Nature's equivalent of dynamic combinatorial chemistry. Graphical Abstract: The importance of intramolecular salt bridges for the formation and stability of glutathione-coordinated [2Fe-2S] cluster was probed through kinetic studies of the dependence of cluster hydrolysis on solution ionic strength. Results indicate that the stability of the cluster and the rate of cluster degradation depend on charge density, hydrated ionic radius, and hydration energy. Consistent with the modified Debye-Hückel equation and counterion screening effect, these results suggest that interactions between glutathione molecules in the [2Fe-2S](GS)4 cluster are promoted by salt bridge formation and the resulting macrocyclic effect. SBIC, 2015 Iron-sulfur cluster nationallicence Cluster assembly nationallicence Glutathione nationallicence Debye-Hückel nationallicence Salt bridge nationallicence C F : Correction factor nationallicence ESI-MS : Electrospray ionization mass spectrometry nationallicence GSH : Glutathione nationallicence Δ H m,hyd : Molar hydration enthalpy nationallicence hISU : Human iron-sulfur cluster assembly enzyme nationallicence rds : Rate determining step nationallicence SI : Système internationale nationallicence Li Jingwei Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, 43210, Columbus, OH, USA aut Pearson Stephen The Ohio State University Biophysics Program, The Ohio State University, 484 West 12th Avenue, 43210, Columbus, OH, USA aut Fenk Kevin Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, 43210, Columbus, OH, USA aut Cowan J. Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, 43210, Columbus, OH, USA aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/8(2015-12-01), 1221-1227 0949-8257 20:8<1221 2015 20 775 https://doi.org/10.1007/s00775-015-1301-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1301-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Jingwei Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, 43210, Columbus, OH, USA aut NATIONALLICENCE 700 1- Pearson Stephen The Ohio State University Biophysics Program, The Ohio State University, 484 West 12th Avenue, 43210, Columbus, OH, USA aut NATIONALLICENCE 700 1- Fenk Kevin Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, 43210, Columbus, OH, USA aut NATIONALLICENCE 700 1- Cowan J. Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, 43210, Columbus, OH, USA aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/8(2015-12-01), 1221-1227 0949-8257 20:8<1221 2015 20 775