7az5 | pdb_00007az5

DNA polymerase sliding clamp from Escherichia coli with peptide 47 bound

spinqualitylabelsall models 7az5, resolution 1.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7az5 is a 8 chain structure with sequence from Escherichia coli 2-427-07_S4_C3 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.87Å Ligands: ACE, ALC, OIC, PEG, PG4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase 3D structures

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