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===Introduction===
===Introduction===
In this figure <scene name='Sandbox_Reserved_430/Cisplatin_intro/4'>cisplatin</scene> is <scene name='Sandbox_Reserved_430/Cisplatin_intro/7'>bound</scene> 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.  
In this figure <scene name='Sandbox_Reserved_430/Cisplatin_intro/4'>cisplatin</scene> is bound 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.   
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===
===Overall Structure===
The original view shows a double stranded DNA helix and the cisplatin ligand. 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===


===Additional Features==
===Additional Features===
 
Cisplatin Binds to DNA by a a 1,2 intrastrand DNA cross link.
The distortion to the structure of DNA caused by the cisplatin cross links allows the recognition of HMG domain protiens to bind to the DNA.
DNA containing platinum lesions  show a shift from right handed B to left hand Z DNA
A<scene name='Sandbox_Reserved_430/1a84_20_21/1'>kink</scene> around the platinum coordination site (20,21) appears in green here. This is caused by the Cisplatin cross link.


===Credits===
===Credits===
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Introduction - Gina Lein
Introduction - Gina Lein


Overall Structure - name of team member
Overall Structure - Greg Keohane


Drug Binding Site - name of team member
Drug Binding Site - name of team member


Additional Features - Nicole Hofstetter
Additional Features - name of team member


===References===
===References===
<references/>
<references/>

Revision as of 05:10, 5 March 2012

Cisplatin

Drag the structure with the mouse to rotate
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.


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Cisplatin-DNA complex- 1a84

Introduction

In this figure cisplatin is bound 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. 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

Additional Features

Credits

Introduction - Gina Lein

Overall Structure - Greg Keohane

Drug Binding Site - name of team member

Additional Features - name of team member

References