5agv: Difference between revisions
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<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 [ | <table><tr><td colspan='2'>[[5agv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv] and [https://en.wikipedia.org/wiki/Streptomyces_muensis Streptomyces muensis]. 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 [https://proteopedia.org/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 | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=NA:SODIUM+ION'>NA</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5agv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5agv OCA], [https://pdbe.org/5agv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5agv RCSB], [https://www.ebi.ac.uk/pdbsum/5agv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5agv ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/DPO3B_MYCTU DPO3B_MYCTU] DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. This DNA polymerase also exhibits 3' to 5' exonuclease activity. The beta chain is required for initiation of replication once it is clamped onto DNA, it slides freely (bidirectional and ATP-independent) along duplex DNA (By similarity). | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[DNA polymerase|DNA polymerase]] | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Streptomyces | [[Category: Streptomyces muensis]] | ||
[[Category: Heinz | [[Category: Heinz DW]] | ||
[[Category: Kling | [[Category: Kling A]] | ||
[[Category: Lukat | [[Category: Lukat P]] | ||
[[Category: Mueller | [[Category: Mueller R]] | ||
Revision as of 07:58, 25 May 2023
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
FunctionDPO3B_MYCTU DNA polymerase III is a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria. This DNA polymerase also exhibits 3' to 5' exonuclease activity. The beta chain is required for initiation of replication once it is clamped onto DNA, it slides freely (bidirectional and ATP-independent) along duplex DNA (By similarity). 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
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