Proteins lead-protein interactions

Goering PL. 1993. Lead-protein interactions as a basis for lead toxicity. Neurotoxicology 14 45-60. 

It has been observed (HI) that, when bathing the agar gels in saline, parts of the albumin are swept on to the cationic side and form new lines of precipitate. Finally, old sera, where enzymatic action has set in, must be avoided, as proteolytic degradation of proteins leads to interactions and lowers the general dispersion of the serum. If all such cases had been carefully discarded, many a doubtful line would not have been discussed in the literature ... 

Lead bound to cysteine residues in proteins results in the appearance of several intense absorption bands in the ultraviolet (UV) region of the absorption spectrum (37, 50-53, 89, 90). These absorption bands have been used successfully in our laboratory and elsewhere to monitor the stability of lead-protein interactions (37, 53) (discussed in detail in Sections IV and VI) but there has not yet been a detailed study of the electronic origin of these bands. Here, we review previous work on the theory of CT transitions in related systems and then apply those ideas to the spectra observed for lead in proteins. 

SUMOylation. Figure 1 SUMOylation is a reversible and regulated process. Target protein modification by SUMO can be initiated and terminated by different cues. Sumoylation leads to changes in the behavior of the modified protein, for example, different cellular localization, enhanced/reduced activity, or increased stability. These changes are due to alterations either in protein interactions or protein folding. 

Experimental screening established that compound 42 shown in Fig. 8.11 disrupts ZipA-FtsZ protein-protein interaction. However, previous studies suggested potential issues with toxicity associated with this class of compounds. Additionally such amine-substituted pyridyl-pyrimidines are heavily patented in the context of kinase inhibition. Both of these factors limit the scope of the subsequent lead optimization process, to transform this compound into a viable drug. Knowledge that compound 42 was a micromolar inhibitor of ZipA-FtsZ was exploited by searching for molecules that were similar in shape. 

New developments in immobilization surfaces have lead to the use of SPR biosensors to monitor protein interactions with lipid surfaces and membrane-associated proteins. Commercially available (BIACORE) hydrophobic and lipophilic sensor surfaces have been designed to create stable membrane surfaces. It has been shown that the hydrophobic sensor surface can be used to form a lipid monolayer (Evans and MacKenzie, 1999). This monolayer surface can be used to monitor protein-lipid interactions. For example, a biosensor was used to examine binding of Src homology 2 domain to phosphoinositides within phospholipid bilayers (Surdo et al., 1999). In addition, a lipophilic sensor surface can be used to capture liposomes and form a lipid bilayer resembling a biological membrane. 

The experiments described above indicate that technology is available to couple SPR with mass spectrometry. These methods should be useful for protein-protein interaction mapping. For example, immobilized proteins can be used as hooks for fishing binding partners from complex protein mixtures under native conditions. The coupling of techniques can lead not only to the rapid identification of interacting proteins but will also provide information on the kinetic parameters of the interaction. This approach should serve as an excellent complement to the use of in vivo techniques such as the yeast two-hybrid system. 

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