Insulin crystal growth

Addition of zinc in order to promote Zn-insulin crystal growth (which take longer to disassociate and, hence, longer to leak into the bloodstream from the injection depot site). 

The insulin-like growth factor I receptor is closely related to the insulin receptor. The RTK activity of the IGF-I receptor is regulated by intermolecular autophosphorylation at three sites within the activation loop. The crystal structure of the trisphosphorylated form of IGF-I RTK domain with an ATP analog and a specific peptide substrate showed that autophosphorylation stabilizes the activation loop in a conformation that facilitates catalysis. Furthermore, the structure revealed how... 

Although insulin was first crystallized in 1926, the factors promoting crystal growth were poorly understood and yielded inconsistent results. It was almost 10 years later when researchers discovered that the addition of zinc to a crude extract promoted reproducible crystallization (zinc addition yields a characteristic rhombohedral crystal, the basic crystal unit being the insulin hexamer, stabilized by the two zinc atoms). 

Yip, C.M. Ward, M.D. Atomic force microscopy of insulin single crystals direct visualization of molecules and crystal growth. Biophys. J. 1996, 71 (2), 1071-1078. 

Rom, W.N., Basset, P., Fells, G.A., Nukiwa, T. and Crystal, R.G. (1988). Alveolar macrophages releases an insulin like growth fector 1-type molecule. J. Clin. Invest. 82, 1685-1693. 

The promotion by insulin of glucose uptake by muscle and fat cells (adipocytes), of glycogen deposition in liver and muscle, and its stimulation of growth soon emerged as the purified hormone became available for study. Although insulin was crystallized by Abel in 1926, its primary structure established by Sanger in 1953 (see Chapter 10),... 

They have carried out similar kind of study with BSA also. They have noticed the formation of AU25 along with the Aug intermediate and concluded that the core might be the same but the growth depends completely on the nature of the protein. The above mentioned proteins are bigger (583 amino acid residues) and so it is expected that they can accommodate smaller 1 nm cluster core within. But when the protein size is smaller like insulin, there is a chance that clusters cannot form inside the protein rather multiple proteins can stabilize one core. Such type of studies were done with insulin where clusters were grown uniformly inside micro-crystals of protein and that was proved by depth dependent two-photon excitation spectroscopy and RAMAN spectroscopy but mass spectrum is not available for this specific system. ... 

---