P53-DNA Recognition: Difference between revisions
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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 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>. | 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, the most frequently mutated residue in cancer, for p53-DNA binding. This 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== | |||
The distinct <scene name='Sandbox_Reserved_170/Arg248/2'>shape of the minor groove recognized by Arg248</scene> is due to a transition of the four A/T base pairs of the CATG core elements to a Hoogsteen base pairing geometry. Regions with Hoogsteen base pairs (red) <scene name='Sandbox_Reserved_170/Hg_helix/2'>assume a reduced diameter of the double helix</scene> compared to regions with Watson-Crick base pairs (blue). | |||
<scene name='Group:USC-LCHS/3kmd_wcbp_closeup/1'>WC bps</scene> | <scene name='Group:USC-LCHS/3kmd_wcbp_closeup/1'>WC bps</scene> | ||
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<scene name='Group:USC-LCHS/3kz8_ba_hoogsteencloseup/2'>Hoogsteen geometry</scene> | <scene name='Group:USC-LCHS/3kz8_ba_hoogsteencloseup/2'>Hoogsteen geometry</scene> | ||
=Further Reading= | =Further Reading= | ||
