View source for 4pnu


==E. coli sliding clamp in complex with (R)-6-bromo-9-(2-((R)-1-carboxy-2-phenylethylamino)-2-oxoethyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylic acid==
<StructureSection load='4pnu' size='340' side='right'caption='[[4pnu]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4pnu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_str._K-12_substr._MC4100 Escherichia coli str. K-12 substr. MC4100]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PNU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PNU 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2VD:(2R)-6-BROMO-9-(2-{[(1R)-1-CARBOXY-2-PHENYLETHYL]AMINO}-2-OXOETHYL)-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-2-CARBOXYLIC+ACID'>2VD</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></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=4pnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pnu OCA], [https://pdbe.org/4pnu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pnu RCSB], [https://www.ebi.ac.uk/pdbsum/4pnu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pnu ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The bacterial DNA replication machinery presents new targets for the development of antibiotics acting via novel mechanisms. One such target is the protein-protein interaction between the DNA sliding clamp and the conserved peptide linear motifs in DNA polymerases. We previously established that binding of linear motifs to the Escherichia coli sliding clamp occurs via a sequential mechanism that involves two subsites (I and II). Here, we report the development of small-molecule inhibitors that mimic this mechanism. The compounds contain tetrahydrocarbazole moieties as "anchors" to occupy subsite I. Functional groups appended at the tetrahydrocarbazole nitrogen bind to a channel gated by the side chain of M362 and lie at the edge of subsite II. One derivative induced the formation of a new binding pocket, termed subsite III, by rearrangement of a loop adjacent to subsite I. Discovery of the extended binding area will guide further inhibitor development.

Bacterial Sliding Clamp Inhibitors that Mimic the Sequential Binding Mechanism of Endogenous Linear Motifs.,Yin Z, Whittell LR, Wang Y, Jergic S, Ma C, Lewis PJ, Dixon NE, Beck JL, Kelso MJ, Oakley AJ J Med Chem. 2015 Jun 11;58(11):4693-702. doi: 10.1021/acs.jmedchem.5b00232. Epub , 2015 May 28. PMID:25970224<ref>PMID:25970224</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4pnu" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Escherichia coli str. K-12 substr. MC4100]]
[[Category: Large Structures]]
[[Category: Oakley AJ]]
[[Category: Yin Z]]