Sandbox Reserved 430: Difference between revisions
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<scene name='Sandbox_Reserved_430/Cisplatin_minor_groove_distanc/1'>Cisplatin minor groove</scene> | <scene name='Sandbox_Reserved_430/Cisplatin_minor_groove_distanc/1'>Cisplatin minor groove</scene> | ||
This deformation of the DNA duplex with cisplatin forms important complexes with HMG proteins, such as <font color='orange'>LEF-1</font> and hSRY. Binding of these proteins to the already damaged DNA causes further bending. The <font color='orange'>LEF-1</font> HMG protein structure was determined by experiment and superimposed over the known cisplatin-DNA structure. The best fit was shown be over the portion of the cisplatin-DNA structure containing the platinated guanonsines of the 1,2 intrastrand cross link, the similarity holds a good overlap of RMSD of 3.2A. | This deformation of the DNA duplex with cisplatin forms important complexes with HMG proteins, such as <font color='orange'>LEF-1</font> and hSRY. Binding of these proteins to the already damaged DNA causes further bending. The <font color='orange'>LEF-1</font> HMG protein structure was determined by experiment and superimposed over the known cisplatin-DNA structure.<ref> Gelasco, Andrew. "NMR solution and structure of DNA Dodecamer Duplex Containing cis-Diammaineplatium" Department of Chemistry, MIT:1998</ref> The best fit was shown be over the portion of the cisplatin-DNA structure containing the platinated guanonsines of the 1,2 intrastrand cross link, the similarity holds a good overlap of RMSD of 3.2A. | ||
<scene name='Sandbox_Reserved_430/2lef/1'>Lef-1 Minor groove</scene> | <scene name='Sandbox_Reserved_430/2lef/1'>Lef-1 Minor groove</scene> | ||
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cisplatin –modified DNA may signal the recognition of HMG proteins. | cisplatin –modified DNA may signal the recognition of HMG proteins. | ||
Another important example is the <font color='red'>HMG1</font> protein binding to the Cisplatin complex. This <font color='red'>HMG1</font>protein is known to bind to the Cisplatin DNA minor groove about the hydrophobic kink created by the distortion. Evidence shows that the phenylalanine residue <font color='red'>HMG1</font> protein is essential for <font color='red'>HMG1</font> interaction with DNA. Substitution experiments of the phenylalanine with alanine showed that <font color='red'>HMG1</font>HMG1 binding reduced, therefore <font color='red'>HMG1</font> binding is dependent on the phenylalanine and the hydrophobic notch | Another important example is the <font color='red'>HMG1</font> protein binding to the Cisplatin complex. This <font color='red'>HMG1</font>protein is known to bind to the Cisplatin DNA minor groove about the hydrophobic kink created by the distortion. Evidence shows that the phenylalanine residue <font color='red'>HMG1</font> protein is essential for <font color='red'>HMG1</font> interaction with DNA. <ref>Love, JJ. "Structural basis for DNA bending by the architectural transcription factor LEF-1." PubMed:1995 http://www.rcsb.org/pdb/explore/explore.do?structureId=2LEF</ref>Substitution experiments of the phenylalanine with alanine showed that <font color='red'>HMG1</font>HMG1 binding reduced, therefore <font color='red'>HMG1</font> binding is dependent on the phenylalanine and the hydrophobic notch | ||
<scene name='Sandbox_Reserved_430/Hmg1_to_cisplatin/6'>HMG1 and the hydrophobic notch</scene> | <scene name='Sandbox_Reserved_430/Hmg1_to_cisplatin/6'>HMG1 and the hydrophobic notch</scene> | ||
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