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===Overall Structure=== | ===Overall Structure=== | ||
| - | The original view shows a double stranded DNA helix and the cisplatin ligand. <scene name='Sandbox_Reserved_430/Cisplatin_ligand/1'>Platination bond d(GpG)</scene>. The cisplatin ligand is a cis-diammineplatinum molecule, which is a platinum atom attached to two N7 nitrogen atoms, each apart of a guanine base pair, and two NH3 molecules attached to the other side. They attach to the 6 and 7 guanine base pairs which links the two bases together and alters the bend in the helix by 49 degrees. The guanine still pair with the 18 and 19 cytosine bases. There are no alpha helixs or beta strands because cisplatin works with DNA and not on proteins. | + | The original view shows a double stranded DNA helix and the cisplatin ligand. This molecule is in its Z configuration which means it has a left handed helix. It is much more rare than the common B-DNA which is right handed. The sugar-phosphate backbone has a zigzag pattern due to the alternate stacking of bases in anti-conformation and syn conformation. In Z-DNA only a minor groove is present and the major groove is absent. This DNA form is thought to play a role in the regulation of gene expression, DNA processing events and/or genetic instability.[2] <scene name='Sandbox_Reserved_430/Cisplatin_ligand/1'>Platination bond d(GpG)</scene>. The cisplatin ligand is a cis-diammineplatinum molecule, which is a platinum atom attached to two N7 nitrogen atoms, each apart of a guanine base pair, and two NH3 molecules attached to the other side. They attach to the 6 and 7 guanine base pairs which links the two bases together and alters the bend in the helix by 49 degrees. The guanine still pair with the 18 and 19 cytosine bases. There are no alpha helixs or beta strands because cisplatin works with DNA and not on proteins. |
===Binding Interactions=== | ===Binding Interactions=== | ||
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===References=== | ===References=== | ||
<references/> | <references/> | ||
| + | 1.↑ 2.0 2.1 2.2 2.3 2.4 2.5 Wang G, Vasquez KM. Z-DNA, an active element in the genome. Front Biosci. 2007 May 1;12:4424-38. PMID:17485386 | ||
Revision as of 15:29, 5 March 2012
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| This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439. |
Contents |
Cisplatin-DNA complex- 1a84
Introduction
In this figure is to a 12 base pair double stranded DNA, creating a 49° bend with an overall helix bend of 78°. This bend in the DNA is crucial to cisplatin’s role as an anticancer drug. Cisplatin, cis-PtCl2(NH3)2, is a chemotherapy drug, administered intravenously, used in the treatment of various types of cancer. This platinum-based drug acts in vivo by binding to two consecutive adjacent guanine bases in DNA. The binding of cisplatin bends the DNA, allowing for HMG-protein to bind. Once the HMG-protein is bound, de-stacking of the nucleotide base pairs occurs, which in turn kinks the DNA. With the HMG-protein bound to the DNA, the cell cannot properly repair the DNA, leading to apoptosis.
Overall Structure
The original view shows a double stranded DNA helix and the cisplatin ligand. This molecule is in its Z configuration which means it has a left handed helix. It is much more rare than the common B-DNA which is right handed. The sugar-phosphate backbone has a zigzag pattern due to the alternate stacking of bases in anti-conformation and syn conformation. In Z-DNA only a minor groove is present and the major groove is absent. This DNA form is thought to play a role in the regulation of gene expression, DNA processing events and/or genetic instability.[2] . The cisplatin ligand is a cis-diammineplatinum molecule, which is a platinum atom attached to two N7 nitrogen atoms, each apart of a guanine base pair, and two NH3 molecules attached to the other side. They attach to the 6 and 7 guanine base pairs which links the two bases together and alters the bend in the helix by 49 degrees. The guanine still pair with the 18 and 19 cytosine bases. There are no alpha helixs or beta strands because cisplatin works with DNA and not on proteins.
Binding Interactions
-Cisplatin binds with duplex DNA strands causing them to bend and distort.
-This distortion or unwinding of the helix towards the major groove allows the minor groove to be left open.
-The minor groove is associated with HMG-domain protein recognition, and the bending of the the helix allows for interactions with the HMG protein.
Additional Features
Cisplatin 1,2 intrastrand cross links DNA.
It distorts the DNA duplex and allows recognition and binding by HMG-domain proteins.
The interstrand cross link (18,19) was found to have created a localized change in DNA from being right handed B DNA to left handed Z- DNA.
The 1,2 intrastrand cross links shows that the double helix forms a major groove at the site (20,21), the platinum coordination site.
Credits
Introduction - Gina Lein
Overall Structure - Greg Keohane
Drug Binding Site - Louis Pires
Additional Features - Nicole Hofstetter
References
1.↑ 2.0 2.1 2.2 2.3 2.4 2.5 Wang G, Vasquez KM. Z-DNA, an active element in the genome. Front Biosci. 2007 May 1;12:4424-38. PMID:17485386
