7az5: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==== | ==DNA polymerase sliding clamp from Escherichia coli with peptide 47 bound== | ||
<StructureSection load='7az5' size='340' side='right'caption='[[7az5]]' scene=''> | <StructureSection load='7az5' size='340' side='right'caption='[[7az5]], [[Resolution|resolution]] 1.87Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7az5]] 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=7AZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AZ5 FirstGlance]. <br> | ||
</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=7az5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7az5 OCA], [https://pdbe.org/7az5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7az5 RCSB], [https://www.ebi.ac.uk/pdbsum/7az5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7az5 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.87Å</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=OIC:OCTAHYDROINDOLE-2-CARBOXYLIC+ACID'>OIC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=7az5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7az5 OCA], [https://pdbe.org/7az5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7az5 RCSB], [https://www.ebi.ac.uk/pdbsum/7az5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7az5 ProSAT]</span></td></tr> | |||
</table> | </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 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7az5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Escherichia coli 2-427-07_S4_C3]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[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]] | |||
Latest revision as of 15:19, 1 February 2024
DNA polymerase sliding clamp from Escherichia coli with peptide 47 boundDNA polymerase sliding clamp from Escherichia coli with peptide 47 bound
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 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||