Sandbox Reserved 199: Difference between revisions
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In 1988, Udgaonkar et al. used 2-dimensional 1H NMR to study bovine pancreatic Ribonuclease and examined protein folding dynamics, which supported the framework model protein folding mechanism. | In 1988, Udgaonkar et al. used 2-dimensional 1H NMR to study bovine pancreatic Ribonuclease and examined protein folding dynamics, which supported the framework model protein folding mechanism. | ||
===Medical Significance=== | |||
Ribonucleases which can prevent inhibition by ribonuclease inhibitors have been looked at as potential anti-tumor agents for some time now. In fact, Onconase ® (an RNase A homolog from the green leopard frog) is already in clinical trials due to its toxicity to cancer cells. However, due to possible immunogenicity of the frog enzyme, much effort has been focused on developing a mutated human RNase which can prevent inhibition by human ribonuclease inhibitor (HcRI). HcRI selectively binds to human pancreatic RNase (RNase 1) and impedes its enzymatic activity. Without sufficient degradation of mRNA, the cell undergoes enhanced gene expression and can lead to cancer. Correctly characterizing RNase 1’s structure and binding specificity via NMR will prove vital to the development of RNase-based anti-cancer treatments. | |||
==NMR Study of Ribonuclease Folding Dynamics== | ==NMR Study of Ribonuclease Folding Dynamics== | ||
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Interestingly, the global correlation time of RNase 1 was shown to be much longer than what is expected for a 13.7 kDa monomer (10ns compared to 6-7ns). This shows that under NMR sample conditions, the RNase1 undergoes dimerization forming a monomer/dimer equilibrium. Because dimerization has shown to have a significant effect on enzyme activity in bovine RNases, certain mutated RNase 1’s which show increased dimerization may be potential anti-cancer therapeutics. | Interestingly, the global correlation time of RNase 1 was shown to be much longer than what is expected for a 13.7 kDa monomer (10ns compared to 6-7ns). This shows that under NMR sample conditions, the RNase1 undergoes dimerization forming a monomer/dimer equilibrium. Because dimerization has shown to have a significant effect on enzyme activity in bovine RNases, certain mutated RNase 1’s which show increased dimerization may be potential anti-cancer therapeutics. | ||
== References == | == References == | ||
