Different Oligomeric States of the Tumor Suppressor p53 Show Identical Binding Behavior Towards the S100beta Homodimer
The tumor suppressor protein p53 is a transcription factor that is referred to as the “guardian of the genome” and plays an important role in cancer development. P53 is active as a homotetramer; the S100β homodimer binds to the intrinsically disordered C-terminus of p53 affecting its transcriptional activity. The p53/S100β complex is regarded as highly…
Computer-Aided Engineering of Staphylokinase Toward Enhanced Affinity and Selectivity for Plasmin
Cardio- and cerebrovascular diseases are leading causes of death and disability, resulting in one of the highest socio-economic burdens of any disease type. The discovery of bacterial and human plasminogen activators and their use as thrombolytic drugs have revolutionized treatment of these pathologies. Fibrin-specific agents have an advantage over non-specific factors because of lower rates…
Characterisation of a unique linker segment of the Plasmodium falciparum cytosol localised Hsp110 chaperone
Plasmodium falciparum expresses two essential cytosol localised chaperones; PfHsp70-1 and PfHsp70-z. PfHsp70-z (Hsp110 homologue) is thought to facilitate nucleotide exchange function of PfHsp70-1. PfHsp70-1 is a refoldase, while PfHsp70-z is restricted to holdase chaperone function. The structural features delineating functional specialisation of these chaperones remain unknown. Notably, PfHsp70-z possesses a unique linker segment which could account for its distinct functions. Using recombinant forms…
Kinetic and thermodynamic insights into interaction of albumin with piperacillin: Spectroscopic and molecular modeling approaches
The current study investigated the binding of BSA and piperacillin at multifarious concentrations (1 e128 mM) along with four different temperatures. To do this, three sensitive methods were employed including surface plasmon resonance (SPR), fluorescence spectroscopy and molecular docking (MD). In the SPR method, BSA immobilized on the carboxymethyl dextran (CMD) hydrogel sensor chip through NHS/EDC activation. The…
Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation
Damage-associated molecular patterns (DAMPs) are molecules that can be actively or passively released by injured tissues and that activate the immune system. Here we show that nicotinate phosphoribosyltransferase (NAPRT), detected by antibody-mediated assays and mass spectrometry, is an extracellular ligand for Toll-like receptor 4 (TLR4) and a critical mediator of inflammation, acting as a DAMP. Exposure of human and…