P53-DNA Recognition: Difference between revisions
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===DNA Backbone Contact=== | ===DNA Backbone Contact=== | ||
Another arginine residue, <scene name='Sandbox_Reserved_170/Arg273/2'>Arg273 contacts the phosphodiester backbone</scene> and seems to be important for p53-DNA binding. Moreover, Arg273 is the second most common missense mutation in human cancer (Figure 2). | Another arginine residue, <scene name='Sandbox_Reserved_170/Arg273/2'>Arg273, contacts the phosphodiester backbone</scene> and seems to be important for p53-DNA binding. Moreover, Arg273 is the second most common missense mutation in human cancer (Figure 2). | ||
[[Image:Kitayner-etal-Figure7.jpg|thumb|right|400px|Figure 7: DNA shape readout of narrow minor groove regions with enhanced electrostatic potential by Arg248<ref name='kitayner'/>. Nature Publishing Group has provided permission for usage of this figure.]] | [[Image:Kitayner-etal-Figure7.jpg|thumb|right|400px|Figure 7: DNA shape readout of narrow minor groove regions with enhanced electrostatic potential by Arg248<ref name='kitayner'/>. Nature Publishing Group has provided permission for usage of this figure.]] | ||
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===Minor Groove Shape Readout=== | ===Minor Groove Shape Readout=== | ||
Most commonly, however, the residue Arg248 is found mutated in human tumors. <scene name='Sandbox_Reserved_170/Arg248/2'>Arg248 contacts the minor groove</scene> although it does not usually form hydrogen bonds with the bases. Arg248 was shown to recognize regions of narrow minor groove associated with enhanced negative electrostatic potential<ref name='kitayner'/>. This observation provides a novel molecular explanation of the importance Arg248 | Most commonly, however, the residue Arg248 is found mutated in human tumors. <scene name='Sandbox_Reserved_170/Arg248/2'>Arg248 contacts the minor groove</scene> although it does not usually form hydrogen bonds with the bases. Arg248 was shown to recognize regions of narrow minor groove associated with enhanced negative electrostatic potential<ref name='kitayner'/>. This observation provides a novel molecular explanation of the importance of Arg248 for p53-DNA binding and its role in cancer. The described mechanism known as '''shape readout''' was found to be broadly employed by arginine residues<ref name="nature">Rohs R, West SM, Sosinsky A, Liu P, Mann RS, Honig B. The role of DNA shape in protein-DNA recognition. Nature. 2009;461(7268):1248-53.</ref>. | ||
==Hoogsteen vs. Watson-Crick Base Pair in p53 Binding Sites== | ==Hoogsteen vs. Watson-Crick Base Pair in p53 Binding Sites== | ||