5fpr

Structure of Bacterial DNA Ligase with small-molecule ligand pyrimidin-2-amine (AT371) in an alternate binding site.

spinqualitylabelsall models 5fpr, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5fpr is a 1 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: LGA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DNLJ_STAAU Publication Abstract from PubMed Proteins need to be tightly regulated as they control biological processes in most normal cellular functions. The precise mechanisms of regulation are rarely completely understood but can involve binding of endogenous ligands and/or partner proteins at specific locations on a protein that can modulate function. Often, these additional secondary binding sites appear separate to the primary binding site, which, for example for an enzyme, may bind a substrate. In previous work, we have uncovered several examples in which secondary binding sites were discovered on proteins using fragment screening approaches. In each case, we were able to establish that the newly identified secondary binding site was biologically relevant as it was able to modulate function by the binding of a small molecule. In this study, we investigate how often secondary binding sites are located on proteins by analyzing 24 protein targets for which we have performed a fragment screen using X-ray crystallography. Our analysis shows that, surprisingly, the majority of proteins contain secondary binding sites based on their ability to bind fragments. Furthermore, sequence analysis of these previously unknown sites indicate high conservation, which suggests that they may have a biological function, perhaps via an allosteric mechanism. Comparing the physicochemical properties of the secondary sites with known primary ligand binding sites also shows broad similarities indicating that many of the secondary sites may be druggable in nature with small molecules that could provide new opportunities to modulate potential therapeutic targets. Detection of secondary binding sites in proteins using fragment screening.,Ludlow RF, Verdonk ML, Saini HK, Tickle IJ, Jhoti H Proc Natl Acad Sci U S A. 2015 Dec 11. pii: 201518946. PMID:26655740 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DNA ligase 3D structures

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