4n95: Difference between revisions
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==E. coli sliding clamp in complex with 5-chloroindoline-2,3-dione== | ==E. coli sliding clamp in complex with 5-chloroindoline-2,3-dione== | ||
<StructureSection load='4n95' size='340' side='right' caption='[[4n95]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='4n95' size='340' side='right'caption='[[4n95]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4n95]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4n95]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N95 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2HQ:5-CHLORO-1H-INDOLE-2,3-DIONE'>2HQ</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2HQ:5-CHLORO-1H-INDOLE-2,3-DIONE'>2HQ</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=4n95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n95 OCA], [https://pdbe.org/4n95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n95 RCSB], [https://www.ebi.ac.uk/pdbsum/4n95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n95 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/DPO3B_ECOLI DPO3B_ECOLI] 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. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 4n95" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4n95" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli K-12]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Oakley | [[Category: Oakley AJ]] | ||
[[Category: Yin | [[Category: Yin Z]] | ||
Revision as of 11:15, 11 January 2023
E. coli sliding clamp in complex with 5-chloroindoline-2,3-dioneE. coli sliding clamp in complex with 5-chloroindoline-2,3-dione
Structural highlights
FunctionDPO3B_ECOLI 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. Publication Abstract from PubMedThe bacterial sliding clamp (SC), also known as the DNA polymerase III beta subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 mug/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity. Discovery of lead compounds targeting the bacterial sliding clamp using a fragment-based approach.,Yin Z, Whittell LR, Wang Y, Jergic S, Liu M, Harry EJ, Dixon NE, Beck JL, Kelso MJ, Oakley AJ J Med Chem. 2014 Mar 27;57(6):2799-806. doi: 10.1021/jm500122r. Epub 2014 Mar 18. PMID:24592885[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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