Structural distortion can each be addressed through

Info icon This preview shows pages 410–412. Sign up to view the full content.

View Full Document Right Arrow Icon
structural distortion can each be addressed through the study of models in comparison with the native proteins.
Image of page 410

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
I. IRON-SULFUR PROTEINS AND MODELS 391 H. Core Extrusion/Cluster Displacement Reactions Synthetic model-system work led to the realization that the cluster cores can exist outside the protein and undergo relatively facile ligand-exchange reac- tions. 128 This behavior of the purely inorganic complexes allowed core extrusion reactions 128,144 to be developed. The basic assumption behind these reactions is that the cluster core retains its integrity when it is substituted by low-MW thio- lates, especially aryl thiolates, which replace the cysteinyl ligands that bind it to the protein. In order to free the cluster from the protein, one must at least partially denature the protein, usually by using ~80 percent aqueous solution of a polar aprotic solvent, such as DMSO or HMPA. The resulting inorganic clus- ters can be identified and quantified by measurement of their characteristic elec- tronic absorption or NMR spectra. An alternative approach involves transferal of the unknown cluster in question to an apoprotein that binds a cluster of known type. 145 Since the IFe, 2Fe, and 4Fe sites are each usually bound to the protein by four cysteine residues, it is perhaps not surprising that there have been reports 58 of interconversion of cluster types bound to a given protein. Specifically, in 90 percent aqueous DMSO, the single Fe site in rubredoxin from C. pasteurianum is converted to an Fe4S4 cluster by the addition of sodium sulfide, ferrous chlo- ride, and ferric chloride in ratio 4: 2: 1. Presumably the spacing and geometric disposition of the cysteines are suitable to bind a single Fe or the Fe4S4 cluster, which is readily formed under the reaction conditions. Another example of clus- ter rearrangement involves the three-iron center discussed below that does not extrude as an Fe3S4 center. Rather, at least under certain conditions, the Fe3Sx center rearranges to form Fe2S2 centers. 146 The facile interconversion of the Fe clusters demonstrated the lability of Fe-S systems, and indicates that caution must be exercised in interpreting the results of cluster-displacement reactions. Three-iron centers are a comparatively recent finding,119,146 and the full scope of their distribution is not yet known. Although they have now been confirmed in dozens of proteins, it often remains uncertain what physiological role these centers play. Indeed, since Fe3S4 centers can be produced as an artifact upon oxidation of Fe4S4 centers, it has been suggested that 3Fe centers may not be truly physiological, and could be side products of aerobic protein isolation. This caveat notwithstanding, the 3Fe sites are being found in more and more proteins and enzymes. Their physiological raison d' etre may be more subtle than that of their 1, 2, and 4Fe cousins; we should certainly try to find out more about them.
Image of page 411
Image of page 412
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern