View source for 7azc


==DNA polymerase sliding clamp from Escherichia coli with peptide 22 bound==
<StructureSection load='7azc' size='340' side='right'caption='[[7azc]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7azc]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_2-427-07_S4_C3 Escherichia coli 2-427-07_S4_C3] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AZC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AZC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALC:2-AMINO-3-CYCLOHEXYL-PROPIONIC+ACID'>ALC</scene>, <scene name='pdbligand=CML:(2S)-2-{[(2R)-2-AMINO-2-CARBOXYETHYL]SULFANYL}BUTANEDIOIC+ACID'>CML</scene>, <scene name='pdbligand=GLN:GLUTAMINE'>GLN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QU8:~{N}-(4-methoxyphenyl)methanamide'>QU8</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=7azc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7azc OCA], [https://pdbe.org/7azc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7azc RCSB], [https://www.ebi.ac.uk/pdbsum/7azc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7azc 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.
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== Publication Abstract from PubMed ==
The bacterial DNA sliding clamp (SC), or replication processivity factor, is a promising target for the development of novel antibiotics. We report a structure-activity relationship study of a new series of peptides interacting within the Escherichia coli SC ((Ec)SC) binding pocket. Various modifications were explored including N-alkylation of the peptide bonds, extension of the N-terminal moiety, and introduction of hydrophobic and constrained residues at the C-terminus. In each category, single modifications were identified that increased affinity to (Ec)SC. A combination of such modifications yielded in several cases to a substantially increased affinity compared to the parent peptides with K(d) in the range of 30-80 nM. X-ray structure analysis of 11 peptide/(Ec)SC co-crystals revealed new interactions at the peptide-protein interface (i.e., stacking interactions, hydrogen bonds, and hydrophobic contacts) that can account for the improved binding. Several compounds among the best binders were also found to be more effective in inhibiting SC-dependent DNA synthesis.

Iterative Structure-Based Optimization of Short Peptides Targeting the Bacterial Sliding Clamp.,Monsarrat C, Compain G, Andre C, Engilberge S, Martiel I, Olieric V, Wolff P, Brillet K, Landolfo M, Silva da Veiga C, Wagner J, Guichard G, Burnouf DY J Med Chem. 2021 Dec 9;64(23):17063-17078. doi: 10.1021/acs.jmedchem.1c00918. , Epub 2021 Nov 22. PMID:34806883<ref>PMID:34806883</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7azc" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli 2-427-07_S4_C3]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Andre C]]
[[Category: Brillet K]]
[[Category: Burnouf DY]]
[[Category: Compain G]]
[[Category: Engilberge S]]
[[Category: Guichard G]]
[[Category: Landolfo M]]
[[Category: Martiel I]]
[[Category: Monsarrat C]]
[[Category: Olieric V]]
[[Category: Silva da Veiga C]]
[[Category: Wagner J]]
[[Category: Wolff P]]