4 research outputs found

    IKKγ mimetic peptides block the resistance to apoptosis associated with KSHV infection

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    Primary effusion lymphoma (PEL) is a lymphogenic disorder associated with KSHV infection. Key to the survival and proliferation of PEL is the canonical NF-kB pathway that becomes constitutively activated following overexpression of the viral oncoprotein ks-vFLIP. This arises from its capacity to form a complex with the modulatory subunit of the IKK kinase, IKKgamma (or NEMO) resulting in the overproduction of proteins that promote cellular survival and prevent apoptosis; both of which are important drivers of tumourigenesis. Using a combination of cell based and biophysical assays together with structural techniques, we show that the observed resistance to cell death is largely independent of autophagy or major death receptor signalling pathways and demonstrate that direct targeting of the ks-vFLIP-IKKgamma interaction both in cells and in vitro can be achieved using IKKgamma mimetic peptides. Our results further reveal that these peptides not only induce cell killing, but potently sensitise PEL to the pro-apoptotic agents tumour necrosis factor alpha and etoposide and are the first to confirm ks-vFLIP as a tractable target for the treatment of PEL and related disorders

    PDBLIG: classification of small molecular protein binding in the Protein Data Bank

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    It is known that proteins can adopt different folds while sharing similar features for recognition of similar substrates or ligands, for example, in the binding sites of enzyme cofactors such as ATP. On the other hand, proteins that have highly flexible binding sites or belong to large and diverse protein families can bind structurally dissimilar ligands, as, for example, in the case of the matrix metalloprotease family. We have developed a database, PDBLIG, that classifies protein domains and ligands. The information stored includes each protein's function, domain class(es), which ligand(s) it binds, and so on. The database can provide valuable knowledge for drug discovery, supporting the answering of questions such as whether the same drug molecule can bind different target protein families and whether these families are related functionally or structurally, which ligand classes (such as metabolites or organic molecules) bind to a particular protein family and whether the ligands are druglike, and which target families bind a wide variety of ligands and whether different ligands are associated with different subfamilies

    Small hiatal hernia and postprandial reflux after vertical sleeve gastrectomy: A multiethnic Asian cohort

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    10.1371/journal.pone.0241847PLoS ONE1511-Nove024184
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