A model for the three-dimensional structure of glucagon |
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Authors: | Alex P Korn FP Ottensmeyer |
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Institution: | 1. Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada M4X 1K9;2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M4X 1K9 |
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Abstract: | A literature search on the structural aspects of glucagon in dilute aqueous solution has been undertaken. We have found that a compact, well-defined structure must exist and propose a model for that structure. In doing so, care was taken to distinguish between the raw data themselves and the interpretations drawn from them, and to bring about a model consistent with as much of the data as possible. The model building was performed on Corey-Pauling-Koltun (CPK) space-filling models using secondary structure prediction rules, experimental data such as fluorescence quenching, circular dichroism, NMR and high resolution dark field electron microscopy, and was guided by a hierarchy of intramolecular interactions which places hydrophobic bonding first and hydrogen bonding second. This last criterion places a strict requirement on the model-building to maximize contacts among complementary hydrophobic surfaces; this means that no empty spaces are allowed inside the folded molecule. The resultant model is consistent with all the relevant data. Furthermore, as demanded by any structure building exercise, the model suggests structure-function relationships. One of the predictions drawn from the structure—the binding of guanosine-5′-triphosphate (GTP)—has been confirmed by a preliminary experiment (reported elsewhere). Another aspect of the structure suggests a subtle mechanism for allostery. |
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