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4pnu

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Revision as of 14:25, 29 March 2017

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

Structural highlights

4pnu is a 2 chain structure with sequence from Escherichia coli str. k-12 substr. mc4100. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	4ovf, 4ovg, 4ovh, 4pnv, 4pnw
Gene:	BN896_3391, dnaN (Escherichia coli str. K-12 substr. MC4100)
Activity:	DNA-directed DNA polymerase, with EC number 2.7.7.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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]

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4pnu"

@@ Line 1: / Line 1: @@
 ==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=''>
@@ Line 7: / Line 8: @@
 <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=4pnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pnu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pnu RCSB], [http://www.ebi.ac.uk/pdbsum/4pnu PDBsum]</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=4pnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pnu OCA], [http://pdbe.org/4pnu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pnu RCSB], [http://www.ebi.ac.uk/pdbsum/4pnu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pnu ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 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==

4pnu

From Proteopedia

Revision as of 14:25, 29 March 2017

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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