3q4l: Difference between revisions
New page: '''Unreleased structure''' The entry 3q4l is ON HOLD Authors: Wolff, P., Olieric, V., Briand, J.P., Chaloin, O., Dejaegere, A., Dumas, P., Ennifar, E., Guichard, G., Wagner, J., Burnouf... |
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The | ==Structure of a small peptide ligand bound to E.coli DNA sliding clamp== | ||
<StructureSection load='3q4l' size='340' side='right'caption='[[3q4l]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3q4l]] is a 4 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=3Q4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q4L 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]] 1.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ALC:2-AMINO-3-CYCLOHEXYL-PROPIONIC+ACID'>ALC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZCL:3,4-DICHLORO-L-PHENYLALANINE'>ZCL</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=3q4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q4l OCA], [https://pdbe.org/3q4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q4l RCSB], [https://www.ebi.ac.uk/pdbsum/3q4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q4l 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 multimeric DNA sliding clamps confer high processivity to replicative DNA polymerases and are also binding platforms for various enzymes involved in DNA metabolism. These enzymes interact with the clamp through a small peptide that binds into a hydrophobic pocket which is a potential target for the development of new antibacterial compounds. Starting from a generic heptapeptide, we used a structure-based strategy to improve the design of new peptide ligands. Chemical modifications at specific residues result in a dramatic increase of the interaction as measured by SPR and ITC. The affinity of our best hits was improved by 2 orders of magnitude as compared to the natural ligand, reaching 10(-8) M range. The molecular basis of the interactions was analyzed by solving the co-crystal structures of the most relevant peptides bound to the clamp and reveals how chemical modifications establish new contacts and contributes to an increased affinity of the ligand. | |||
Structure-based design of short peptide ligands binding onto the E. coli processivity ring.,Wolff P, Olieric V, Briand JP, Chaloin O, Dejaegere A, Dumas P, Ennifar E, Guichard G, Wagner J, Burnouf DY J Med Chem. 2011 Jul 14;54(13):4627-37. doi: 10.1021/jm200311m. Epub 2011 Jun 9. PMID:21619076<ref>PMID:21619076</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3q4l" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli K-12]] | |||
[[Category: Large Structures]] | |||
[[Category: Briand JP]] | |||
[[Category: Burnouf D]] | |||
[[Category: Chaloin O]] | |||
[[Category: Dejaegere A]] | |||
[[Category: Dumas P]] | |||
[[Category: Ennifar E]] | |||
[[Category: Guichard G]] | |||
[[Category: Olieric V]] | |||
[[Category: Wagner J]] | |||
[[Category: Wolff P]] | |||
Latest revision as of 13:20, 6 November 2024
Structure of a small peptide ligand bound to E.coli DNA sliding clampStructure of a small peptide ligand bound to E.coli DNA sliding clamp
Structural highlights
FunctionDPO3B_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. Publication Abstract from PubMedThe multimeric DNA sliding clamps confer high processivity to replicative DNA polymerases and are also binding platforms for various enzymes involved in DNA metabolism. These enzymes interact with the clamp through a small peptide that binds into a hydrophobic pocket which is a potential target for the development of new antibacterial compounds. Starting from a generic heptapeptide, we used a structure-based strategy to improve the design of new peptide ligands. Chemical modifications at specific residues result in a dramatic increase of the interaction as measured by SPR and ITC. The affinity of our best hits was improved by 2 orders of magnitude as compared to the natural ligand, reaching 10(-8) M range. The molecular basis of the interactions was analyzed by solving the co-crystal structures of the most relevant peptides bound to the clamp and reveals how chemical modifications establish new contacts and contributes to an increased affinity of the ligand. Structure-based design of short peptide ligands binding onto the E. coli processivity ring.,Wolff P, Olieric V, Briand JP, Chaloin O, Dejaegere A, Dumas P, Ennifar E, Guichard G, Wagner J, Burnouf DY J Med Chem. 2011 Jul 14;54(13):4627-37. doi: 10.1021/jm200311m. Epub 2011 Jun 9. PMID:21619076[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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