Sandbox Reserved 426: Difference between revisions
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==Introduction== | ==Introduction== | ||
The intercalation of DNA and drug compounds has been studied thoroughly | The intercalation of DNA and drug compounds has been studied thoroughly; in this case the nucleotide d(CGTACG) was complexed with an anthraquinone derivative. This derivative, 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione, provided researchers with the information needed to solve <scene name='48/483883/Rainbow_sheet/1'>the structure of the complex</scene> using X-Ray crystallography. Along with the structure, the important forces involved in binding were analyzed and described as heavily reliant on cations. Furthermore, the binding site seems to be specific to anthracene and similar molecules. Therefore, the potential for drug compounds to be carrying by this nucleotide complex requires further research. | ||
==Overall Structure== | ==Overall Structure== | ||
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The 1xcs (model at right) complex is a small, simple globular DNA-drug complex, and as such lacks any traditional protein structures such as secondary beta sheets or alpha helices. The complex consists of two complimentary strands of DNA. A simplified model of 1xcs is shown <scene name='48/483883/Title/4'>here,</scene> with the nitrogenous bases removed for clarity. The deoxyribose backbones can be followed from 5' to 3' following along each strand from blue to red. Note that the strands are antiparallel where they are (hydrogen) bonded. <scene name='48/483883/1xcs_with_side_chains/2'>1xcs with its hydrogen bonding regions displayed (black)</scene> visualizes this bonding in the middle region of the complex, again following each strand from blue to red from 5' to 3' ends. | The 1xcs (model at right) complex is a small, simple globular DNA-drug complex, and as such lacks any traditional protein structures such as secondary beta sheets or alpha helices. The complex consists of two complimentary strands of DNA. A simplified model of 1xcs is shown <scene name='48/483883/Title/4'>here,</scene> with the nitrogenous bases removed for clarity. The deoxyribose backbones can be followed from 5' to 3' following along each strand from blue to red. Note that the strands are antiparallel where they are (hydrogen) bonded. <scene name='48/483883/1xcs_with_side_chains/2'>1xcs with its hydrogen bonding regions displayed (black)</scene> visualizes this bonding in the middle region of the complex, again following each strand from blue to red from 5' to 3' ends. | ||
The 1xcs complex also binds to metal ions in more than one location, which have been shown to be important to the drug's binding ability. Different metal ions may be present, including Na(+) and Co(2+). These metal ions sites are colored pink in <scene name='48/483883/1xcs_with_pink_metal_ions/2'>this</scene> scene. | The 1xcs complex also binds to metal ions in more than one location, which have been shown to be important to the drug's binding ability. Different metal ions may be present, including Na(+) and Co(2+). These metal ions sites are colored pink in <scene name='48/483883/1xcs_with_pink_metal_ions/2'>this</scene> scene. One other metal binding site was noted, which had the ability to bind Ba(2+) (not shown). This barium binding site is believed to strengthen the ability of the O6 site to bind cobalt. This ability to strongly bind metal ions was also important for x-ray crystallographic purposes, as it enabled researchers to form crystals of the complex by relying on interactions between neighboring molecule's binding sites. | ||
==Binding Interactions== | ==Binding Interactions== | ||
Revision as of 23:57, 4 April 2016
| 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. |
Structure of Oligonucleotide/Drug complex (1xcs)[1]Structure of Oligonucleotide/Drug complex (1xcs)[1]
by Michael Beauregard, Annie Burton, Jianlong Li, Daniel Marco, and Nathaneal Park
Student Projects for UMass Chemistry 423 Spring 2016 <StructureSection load='1xcs' size='350' side='right' caption='caption for Molecular Playground (PDB entry 1xcs)' scene=>
IntroductionIntroduction
The intercalation of DNA and drug compounds has been studied thoroughly; in this case the nucleotide d(CGTACG) was complexed with an anthraquinone derivative. This derivative, 1,5-bis[3-(diethylamino)propionamido]anthracene-9,10-dione, provided researchers with the information needed to solve using X-Ray crystallography. Along with the structure, the important forces involved in binding were analyzed and described as heavily reliant on cations. Furthermore, the binding site seems to be specific to anthracene and similar molecules. Therefore, the potential for drug compounds to be carrying by this nucleotide complex requires further research.
Overall StructureOverall Structure
The 1xcs (model at right) complex is a small, simple globular DNA-drug complex, and as such lacks any traditional protein structures such as secondary beta sheets or alpha helices. The complex consists of two complimentary strands of DNA. A simplified model of 1xcs is shown with the nitrogenous bases removed for clarity. The deoxyribose backbones can be followed from 5' to 3' following along each strand from blue to red. Note that the strands are antiparallel where they are (hydrogen) bonded. visualizes this bonding in the middle region of the complex, again following each strand from blue to red from 5' to 3' ends.
The 1xcs complex also binds to metal ions in more than one location, which have been shown to be important to the drug's binding ability. Different metal ions may be present, including Na(+) and Co(2+). These metal ions sites are colored pink in scene. One other metal binding site was noted, which had the ability to bind Ba(2+) (not shown). This barium binding site is believed to strengthen the ability of the O6 site to bind cobalt. This ability to strongly bind metal ions was also important for x-ray crystallographic purposes, as it enabled researchers to form crystals of the complex by relying on interactions between neighboring molecule's binding sites.
Binding InteractionsBinding Interactions
Additional FeaturesAdditional Features
Click to see that the drug binds directly between strands of DNA. This interrupts the expression of this section of DNA. I will then go on to explain how specifically this complex interrupts/changes gene expression.
Quiz Question 1Quiz Question 1
Why is it important for the protein to bind ? A unique site is the __ ion found associated with the , which gives additional strength to the guanine–Co2+–guanine interaction. A Mg2+ B Co2+ C Ba2+ D Mg2+
See AlsoSee Also
CreditsCredits
Introduction - Daniel Marco
Overall Structure - Nathaneal Park
Drug Binding Site - Annie Burton
Additional Features - Michael Beauregard
Quiz Question 1 - Jianlong Li
ReferencesReferences
- ↑ Valls N, Steiner RA, Wright G, Murshudov GN, Subirana JA. Variable role of ions in two drug intercalation complexes of DNA. J Biol Inorg Chem. 2005 Aug;10(5):476-82. Epub 2005 Sep 23. PMID:15926069 doi:10.1007/s00775-005-0655-3