4n95: Difference between revisions

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-{{STRUCTURE_4n95|  PDB=4n95  |  SCENE=  }}
-===E. coli sliding clamp in complex with 5-chloroindoline-2,3-dione===
-==Function==
+==E. coli sliding clamp in complex with 5-chloroindoline-2,3-dione==
-[[http://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.
+<StructureSection load='4n95' size='340' side='right'caption='[[4n95]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</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>
+</table>
+== 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;">
+== Publication Abstract from PubMed ==
+The 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.
-==About this Structure==
+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<ref>PMID:24592885</ref>
-[[4n95]] is a 2 chain structure with sequence from [http://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].
-[[Category: DNA-directed DNA polymerase]]
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Escherichia coli k-12]]
+</div>
-[[Category: Oakley, A J.]]
+<div class="pdbe-citations 4n95" style="background-color:#fffaf0;"></div>
-[[Category: Yin, Z.]]
-[[Category: Dnan]]
+==See Also==
-[[Category: Sliding clamp]]
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
-[[Category: Transferase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Escherichia coli K-12]]
+[[Category: Large Structures]]
+[[Category: Oakley AJ]]
+[[Category: Yin Z]]