4pnu

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

spinqualitylabelsall models 4pnu, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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. Method: X-ray diffraction, Resolution 1.9Å Ligands: 2VD, CA, CL, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA polymerase 3D structures

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