6gim: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
Line 1: Line 1:


==Structure of the DNA duplex d(AAATTT)2 with [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2- yl)amino)benzamide] - (drug JNI18)==
==Structure of the DNA duplex d(AAATTT)2 with [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2- yl)amino)benzamide] - (drug JNI18)==
<StructureSection load='6gim' size='340' side='right' caption='[[6gim]], [[Resolution|resolution]] 1.43&Aring;' scene=''>
<StructureSection load='6gim' size='340' side='right'caption='[[6gim]], [[Resolution|resolution]] 1.43&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6gim]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GIM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GIM FirstGlance]. <br>
<table><tr><td colspan='2'>[[6gim]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GIM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EZK:[4-[(3-chloranyl-4-imidazolidin-2-ylideneazaniumyl-phenyl)carbamoyl]phenyl]-imidazolidin-2-ylidene-azanium'>EZK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.43&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gim OCA], [http://pdbe.org/6gim PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gim RCSB], [http://www.ebi.ac.uk/pdbsum/6gim PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gim ProSAT]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EZK:[4-[(3-chloranyl-4-imidazolidin-2-ylideneazaniumyl-phenyl)carbamoyl]phenyl]-imidazolidin-2-ylidene-azanium'>EZK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6gim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gim OCA], [https://pdbe.org/6gim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gim RCSB], [https://www.ebi.ac.uk/pdbsum/6gim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gim ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Trypanosoma brucei, the causative agent of sleeping sickness (Human African Trypanosomiasis, HAT), contains a kinetoplast with the mitochondrial DNA (kDNA), comprising of &gt;70% AT base pairs. This has prompted studies of drugs interacting with AT-rich DNA, such as the N-phenylbenzamide bis(2-aminoimidazoline) derivatives 1 [4-((4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((4,5-dihydro-1H-imidazol-2-yl)amin o)phenyl)benzamide dihydrochloride] and 2 [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-im idazol-2-yl)amino)benzamide] as potential drugs for HAT. Both compounds show in vitro effects against T. brucei and in vivo curative activity in a mouse model of HAT. The main objective was to identify their cellular target inside the parasite. We were able to demonstrate that the compounds have a clear effect on the S-phase of T. brucei cell cycle by inflicting specific damage on the kinetoplast. Surface plasmon resonance (SPR)-biosensor experiments show that the drug can displace HMG box-containing proteins essential for kDNA function from their kDNA binding sites. The crystal structure of the complex of the oligonucleotide d[AAATTT]2 with compound 1 solved at 1.25 A (PDB-ID: 5LIT) shows that the drug covers the minor groove of DNA, displaces bound water and interacts with neighbouring DNA molecules as a cross-linking agent. We conclude that 1 and 2 are powerful trypanocides that act directly on the kinetoplast, a structure unique to the order Kinetoplastida.
Functional and structural analysis of AT-specific minor groove binders that disrupt DNA-protein interactions and cause disintegration of the Trypanosoma brucei kinetoplast.,Millan CR, Acosta-Reyes FJ, Lagartera L, Ebiloma GU, Lemgruber L, Nue Martinez JJ, Saperas N, Dardonville C, de Koning HP, Campos JL Nucleic Acids Res. 2017 Jun 16. doi: 10.1093/nar/gkx521. PMID:28637278<ref>PMID:28637278</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gim" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Campos, J L]]
[[Category: Large Structures]]
[[Category: Dardonvile, C]]
[[Category: Koning, H P.de]]
[[Category: Millan, C R]]
[[Category: Saperas, N]]
[[Category: Antiparasitic drug]]
[[Category: At-rich dna]]
[[Category: Dna]]
[[Category: Dna binding drug]]
[[Category: Minor groove binding drug]]
[[Category: Trypanosoma brucei]]
[[Category: Trypanosoma brucei]]
[[Category: Campos JL]]
[[Category: Dardonvile C]]
[[Category: Millan CR]]
[[Category: Saperas N]]
[[Category: De Koning HP]]

Latest revision as of 07:33, 1 May 2024

Structure of the DNA duplex d(AAATTT)2 with [N-(3-chloro-4-((4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)-4-((4,5-dihydro-1H-imidazol-2- yl)amino)benzamide] - (drug JNI18)

6gim, resolution 1.43Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=6gim&oldid=4138245"