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Epstein-Barr virus (EBV) is associated with human malignancies, especially those affecting the B cell compartment such as Burkitt lymphoma. The virally encoded homolog of the mammalian pro-survival protein Bcl-2, BHRF1 contributes to viral infectivity and lymphomagenesis. In addition to the pro-apoptotic BH3-only protein Bim, its key target in lymphoid(More)
The influenza virus neuraminidase glycoprotein is a tetramer with a box-shaped head, 100 X 100 X 60 A, attached to a slender stalk. The three-dimensional structure of neuraminidase heads shows that each monomer is composed of six topologically identical beta-sheets arranged in a propeller formation. The tetrameric enzyme has circular 4-fold symmetry(More)
The catalytic sites of influenza virus neuraminidase are located on the upper corners of the box-shaped tetramer that forms the head of the molecule. Antigenic determinants form a nearly-continuous surface across the top of the monomer encircling the catalytic site. Approximately the same number of amino acid sequence changes occurred in these determinants(More)
Like Bcl-2, Mcl-1 is an important survival factor for many cancers, its expression contributing to chemoresistance and disease relapse. However, unlike other prosurvival Bcl-2-like proteins, Mcl-1 stability is acutely regulated. For example, the Bcl-2 homology 3 (BH3)-only protein Noxa, which preferentially binds to Mcl-1, also targets it for proteasomal(More)
The structure of a complex between influenza virus neuraminidase and an antibody displays features inconsistent with the inflexible 'lock and key' model of antigen-antibody binding. The structure of the antigen changes on binding, and that of the antibody may also change; the interaction therefore has some of the character of a handshake.
The crystal structures of a human IgG antibody molecule Kol and a human Fc fragment have been determined at 4-A and 3.4-A resolution respectively, by isomorphous replacement. The electron-density maps were interpreted in terms of immunoglobulin domains based on the Rei and McPC 603 models (Kol) and by model-building (Fc). The Fab parts of Kol have a(More)
The Bcl-2 family regulates induction of apoptosis at the mitochondria. Essential to this regulation are the interactions between Bcl-2 family members, which are mediated by Bcl-2 homology (BH) domains. Vaccinia virus F1L is a unique inhibitor of apoptosis that lacks significant sequence similarity with the Bcl-2 family and does not contain obvious BH(More)
In 2005 a major collaboration in Melbourne, Australia successfully implemented a major medical informatics infrastructure. The convergence of life sciences, healthcare, and information technology is now driving research into the fundamentals of disease causation and toward tailoring individualized treatment. The Molecular Medicine Informatics Model (MMIM)(More)
Subversion of host cell apoptosis is an important survival strategy for viruses to ensure their own proliferation and survival. Certain viruses express proteins homologous in sequence, structure and function to mammalian pro-survival B-cell lymphoma 2 (Bcl-2) proteins, which prevent rapid clearance of infected host cells. In vaccinia virus (VV), the(More)