View source for 4ovh


==E. coli sliding clamp in complex with (R)-6-bromo-9-(2-(carboxymethylamino)-2-oxoethyl)-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylic acid==
<StructureSection load='4ovh' size='340' side='right' caption='[[4ovh]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ovh]] is a 2 chain structure with sequence from [http://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=4OVH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OVH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2VE:(2R)-6-BROMO-9-{2-[(CARBOXYMETHYL)AMINO]-2-OXOETHYL}-2,3,4,9-TETRAHYDRO-1H-CARBAZOLE-2-CARBOXYLIC+ACID'>2VE</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></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ovf|4ovf]], [[4ovg|4ovg]], [[4pnu|4pnu]], [[4pnv|4pnv]], [[4pnw|4pnw]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BN896_3391, dnaN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1403831 Escherichia coli str. K-12 substr. MC4100])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ovh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ovh OCA], [http://pdbe.org/4ovh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ovh RCSB], [http://www.ebi.ac.uk/pdbsum/4ovh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ovh ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/U6NCW5_ECOLI U6NCW5_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 (By similarity).[PIRNR:PIRNR000804] 
<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 4ovh" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase|DNA polymerase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: DNA-directed DNA polymerase]]
[[Category: Escherichia coli str. k-12 substr. mc4100]]
[[Category: Oakley, A J]]
[[Category: Yin, Z]]
[[Category: Dnan]]
[[Category: Poliii beta]]
[[Category: Sliding clamp]]
[[Category: Transferase]]
[[Category: Transferase-transferase inhibitor complex]]