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Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors
Evaluated small-molecule inhibitors of poly-ADP-ribose polymerase (PARP) family proteins showed that the majority of PARP inhibitors bind multiple targets, providing insight into the design of new inhibitors. Expand
Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains.
This work observed that ARTD10 colocalized with ARTD8 and defined its macrodomains 2 and 3 as readers of mono-ADP-ribosylation both in vitro and in cells, and demonstrated the presence of this modification in cells. Expand
Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design.
Comparisons with earlier structures provide a basis for the design of drugs that are specifically directed at either human or bacterial enzymes, suggesting that herbicides targeting GS must be designed with caution. Expand
Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism
It is revealed that BPTES binds to an allosteric pocket at the dimer interface of KGA, triggering a dramatic conformational change of the key loop (Glu312-Pro329) near the catalytic site and rendering it inactive, and the binding mode of BPTes on the hydrophobic pocket explains its specificity to KGA. Expand
Structural Basis for the Inhibition Mechanism of Human Cystathionine γ-Lyase, an Enzyme Responsible for the Production of H2S*
Impairment of the formation or action of hydrogen sulfide (H2S), an endogenous gasotransmitter, is associated with various diseases, such as hypertension, diabetes mellitus, septic and hemorrhagicExpand
Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
A structural and functional analysis of the PARP domain of human PARP-3 in complex with several inhibitors suggests routes for creating isoenzyme-specific PARP inhibitors and highlights key features for potent inhibitor binding. Expand
Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor.
The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and suggests routes for further development of tankyrase inhibitors. Expand
Crystal structure of conserved domains 1 and 2 of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP.
Interestingly, the DDX3X-specific insertion forms a helical element that extends a highly positively charged sequence in a loop, thus increasing the RNA-binding surface of the protein, suggesting that DDx3X is stabilized by AMP and elucidating why AMP was found in the nucleotide-binding pocket. Expand
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitorsExpand
The DEXD/H-box RNA Helicase DDX19 Is Regulated by an α-Helical Switch*S⃞
The crystal structures of DDX19 reveal an α-helix that inserts between the conserved domains of the free protein to negatively regulate ATPase activity, corroborated by biochemical data that confirm an autoregulatory function of the N-terminal region of the protein. Expand