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Saccharomyces WEE1 (Swe1), the only "true" tyrosine kinase in budding yeast, is an Hsp90 client protein. Here we show that Swe1(Wee1) phosphorylates a conserved tyrosine residue (Y24 in yeast Hsp90 and Y38 in human Hsp90alpha) in the N domain of Hsp90. Phosphorylation is cell-cycle associated and modulates the ability of Hsp90 to chaperone a selected(More)
BACKGROUND The conversion of the cellular prion protein (PrP(C)) into the infectious form (PrP(Sc)) is the key event in prion induced neurodegenerations. This process is believed to involve a multi-step conformational transition from an alpha-helical (PrP(C)) form to a beta-sheet-rich (PrP(Sc)) state. In addition to the conformational difference, PrP(Sc)(More)
Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response. ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation. Hsp90 plays an important role in disease states, particularly in cancer, where chaperoning of the mutated and overexpressed oncoproteins is(More)
The absolute values of the one-electron redox potentials of the two quinones (Q(A) and Q(B)) in bacterial photosynthetic reaction centers from Rhodobacter sphaeroides were calculated by evaluating the electrostatic energies from the solution of the linearized Poisson-Boltzmann equation at pH 7.0. The redox potential for Q(A) was calculated to be between(More)
Human immunodeficiency virus type 1 protease (HIV-1 PR) is an essential enzyme in the HIV-1 life cycle. As such, this protein represents a major drug target in AIDS therapy, but emerging resistance to antiretroviral inhibitor cocktails, caused by high viral mutation rates, represents a significant challenge in AIDS treatment. Many mutations are not located(More)
Molecular recognition and ligand binding involving proteins underlie the most important life processes within the cell, such as substrate transport, catalysis, signal transmission, receptor trafficking, gene regulation, switching on and off of biochemical pathways. Despite recent successes in predicting the structures of many protein-substrate complexes,(More)
An increasing number of functional studies of proteins have shown that sequence and structural similarities alone may not be sufficient for reliable prediction of their interaction properties. This is particularly true for proteins recognizing specific antibodies, where the prediction of antibody-binding sites, called epitopes, has proven challenging. The(More)
Computer simulations of proteins, lipids and nucleic acids at equilibrium have become essentially routine. However, the fact remains that complete sampling of conformational space continues to be a bottle-neck in the field. The challenge for the future is to overcome such problems and use computational approaches to understand recognition and spontaneous(More)
Understanding how local protein modifications, such as binding small-molecule ligands, can trigger and regulate large-scale motions of large protein domains is a major open issue in molecular biology. We address various aspects of this problem by analyzing and comparing atomistic simulations of Hsp90 family representatives for which crystal structures of(More)
The molecular chaperone Hsp90 (90 kDa heat-shock protein) mediates many fundamental cellular pathways involved in cell proliferation, cell survival, and cellular stress response. Hsp90 is responsible for the correct conformational development, stability and function in crowded cell environments. Structural and computational biology studies have recently(More)