Sandbox Reserved 199: Difference between revisions
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/* Ribonuclease NMR Structure Versus X-Ray Crystallography Ribonuclease Structure<ref> Santoro, Jorge. "High-resolution Three-dimensional Structure of Ribonuclease A in Solution by Nuclear Magnetic Resonance Spectroscopy." Journal of Molecular Biolog |
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===Overview=== | ===Overview=== | ||
Ribonuclease has been called the most studies enzyme of the 20th century due to its ample availability as well as its significant role within the cell. While the structures of bovine pancreatic ribonuclease (RNase A) and human pancreatic ribonuclease (RNase 1) determined by X-Ray crystallography have been around for some time, the 3D NMR structures of present provide much more information on specific locations of side chain residues and their flexibility. Because NMR does not require a "frozen" crystal structure, NMR imaging can show much more accurate detail into the actual, solution enzyme (folding, flexibility etc.) | Ribonuclease A has served as a model for protein structure and finction, and was the third enzyme whose three-dimensional structure was determined. <ref name="raines"> Raines, Ronald T. "Ribonuclease A." Chemical Reviews; 98, 1045-1065 (1998). Print.</ref>Ribonuclease has been called the most studies enzyme of the 20th century due to its ample availability as well as its significant role within the cell<ref name="raines"/>. While the structures of bovine pancreatic ribonuclease (RNase A) and human pancreatic ribonuclease (RNase 1) determined by X-Ray crystallography have been around for some time, the 3D NMR structures of present provide much more information on specific locations of side chain residues and their flexibility. Because NMR does not require a "frozen" crystal structure, NMR imaging can show much more accurate detail into the actual, solution enzyme (folding, flexibility etc.) | ||
Ribonuclease A and Ribonuclease 1 are both good targets for 3D NMR. Not only are they small proteins (~13 KDa), they also have numerous characteristics that are observable only by NMR, such as internal flexibility and 3D domain swapping. | Ribonuclease A and Ribonuclease 1 are both good targets for 3D NMR. Not only are they small proteins (~13 KDa), they also have numerous characteristics that are observable only by NMR, such as internal flexibility and 3D domain swapping. | ||
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===Medical Significance=== | ===Medical Significance=== | ||
Ribonucleases show specific toxicity to tumor cells. In fact, Onconase ® (an RNase A homolog from the [http://en.wikipedia.org/wiki/Northern_Leopard_Frog Northern Leopard Frog]) is currently in phase IIIb clinical trials for the treatment of malignant mesothelioma. However, due to possible immunogenicity of the frog enzyme, much effort has been focused on developing a cytotoxic human RNase, which evades inhibition by human ribonuclease inhibitor (HRI). HRI selectively binds to human pancreatic RNase (RNase 1) and impedes its enzymatic activity. Correctly characterizing the structure and binding specificity of RNase via NMR could assist in the development of RNase-based anti-cancer treatments. | Ribonucleases show specific toxicity to tumor cells. In fact, Onconase ® (an RNase A homolog from the [http://en.wikipedia.org/wiki/Northern_Leopard_Frog Northern Leopard Frog]) is currently in phase IIIb clinical trials for the treatment of malignant mesothelioma. However, due to possible immunogenicity of the frog enzyme, much effort has been focused on developing a cytotoxic human RNase, which evades inhibition by human ribonuclease inhibitor (HRI). HRI selectively binds to human pancreatic RNase (RNase 1) and impedes its enzymatic activity. Correctly characterizing the structure and binding specificity of RNase via NMR could assist in the development of RNase-based anti-cancer treatments. | ||
==NMR Study of Ribonuclease Folding Dynamics<ref>PMID: 2845278 </ref>== | ==NMR Study of Ribonuclease Folding Dynamics<ref>PMID: 2845278 </ref>== | ||
