5agv: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==The sliding clamp of Mycobacterium tuberculosis in complex with a natural product.== | ==The sliding clamp of Mycobacterium tuberculosis in complex with a natural product.== | ||
<StructureSection load='5agv' size='340' side='right' caption='[[5agv]], [[Resolution|resolution]] 1.93Å' scene=''> | <StructureSection load='5agv' size='340' side='right'caption='[[5agv]], [[Resolution|resolution]] 1.93Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5agv]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Streptomyces_caelicus Streptomyces caelicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AGV FirstGlance]. <br> | <table><tr><td colspan='2'>[[5agv]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu] and [http://en.wikipedia.org/wiki/Streptomyces_caelicus Streptomyces caelicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AGV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AGV FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MLU:N-METHYL-D-LEUCINE'>MLU</scene>, <scene name='pdbligand=MP8:(4R)-4-METHYL-L-PROLINE'>MP8</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=NZC:N-METHYLIDENE-L-THREONINE'>NZC</scene>, <scene name='pdbligand=PH6:(4S)-4-CYCLOHEXYL-L-PROLINE'>PH6</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MLU:N-METHYL-D-LEUCINE'>MLU</scene>, <scene name='pdbligand=MP8:(4R)-4-METHYL-L-PROLINE'>MP8</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=NZC:N-METHYLIDENE-L-THREONINE'>NZC</scene>, <scene name='pdbligand=PH6:(4S)-4-CYCLOHEXYL-L-PROLINE'>PH6</scene></td></tr> | ||
| Line 19: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5agv" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5agv" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[DNA polymerase|DNA polymerase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 24: | Line 27: | ||
</StructureSection> | </StructureSection> | ||
[[Category: DNA-directed DNA polymerase]] | [[Category: DNA-directed DNA polymerase]] | ||
[[Category: Large Structures]] | |||
[[Category: Myctu]] | |||
[[Category: Streptomyces caelicus]] | [[Category: Streptomyces caelicus]] | ||
[[Category: Heinz, D W]] | [[Category: Heinz, D W]] | ||
Revision as of 10:32, 24 April 2019
The sliding clamp of Mycobacterium tuberculosis in complex with a natural product.The sliding clamp of Mycobacterium tuberculosis in complex with a natural product.
Structural highlights
Publication Abstract from PubMedThe discovery of Streptomyces-produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant Mycobacterium tuberculosis has prioritized the need for new drugs. Here we show that new optimized derivatives from Streptomyces-derived griselimycin are highly active against M. tuberculosis, both in vitro and in vivo, by inhibiting the DNA polymerase sliding clamp DnaN. We discovered that resistance to griselimycins, occurring at very low frequency, is associated with amplification of a chromosomal segment containing dnaN, as well as the ori site. Our results demonstrate that griselimycins have high translational potential for tuberculosis treatment, validate DnaN as an antimicrobial target, and capture the process of antibiotic pressure-induced gene amplification. Antibiotics. Targeting DnaN for tuberculosis therapy using novel griselimycins.,Kling A, Lukat P, Almeida DV, Bauer A, Fontaine E, Sordello S, Zaburannyi N, Herrmann J, Wenzel SC, Konig C, Ammerman NC, Barrio MB, Borchers K, Bordon-Pallier F, Bronstrup M, Courtemanche G, Gerlitz M, Geslin M, Hammann P, Heinz DW, Hoffmann H, Klieber S, Kohlmann M, Kurz M, Lair C, Matter H, Nuermberger E, Tyagi S, Fraisse L, Grosset JH, Lagrange S, Muller R Science. 2015 Jun 5;348(6239):1106-12. doi: 10.1126/science.aaa4690. PMID:26045430[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||