Biochemistry and Pharmacology - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/214

Filters

2018 - 2019 1 2020 - 2022 1
Reset filters

Settings
Statistics
Citations
Type: Journal Article × Author: Inouye, Michael × Author: Ascher, David × End date: 2022 ×

Search Results

Now showing 1 - 2 of 2
  • Item
    No Preview Available
    Known allosteric proteins have central roles in genetic disease
    Abrusan, G ; Ascher, DB ; Inouye, M ; Haliloglu, T (PUBLIC LIBRARY SCIENCE, 2022-02)
    Allostery is a form of protein regulation, where ligands that bind sites located apart from the active site can modify the activity of the protein. The molecular mechanisms of allostery have been extensively studied, because allosteric sites are less conserved than active sites, and drugs targeting them are more specific than drugs binding the active sites. Here we quantify the importance of allostery in genetic disease. We show that 1) known allosteric proteins are central in disease networks, contribute to genetic disease and comorbidities much more than non-allosteric proteins, and there is an association between being allosteric and involvement in disease; 2) they are enriched in many major disease types like hematopoietic diseases, cardiovascular diseases, cancers, diabetes, or diseases of the central nervous system; 3) variants from cancer genome-wide association studies are enriched near allosteric proteins, indicating their importance to polygenic traits; and 4) the importance of allosteric proteins in disease is due, at least partly, to their central positions in protein-protein interaction networks, and less due to their dynamical properties.
  • Item
    Thumbnail Image
    Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam
    Holt, KE ; McAdam, P ; Phan, VKT ; Nguyen, TTT ; Dang, TMH ; Nguyen, NL ; Nguyen, HL ; Nguyen, TQN ; Hoang, TH ; Vu, TNH ; Thwaites, G ; Edwards, DJ ; Nath, AP ; Pham, K ; Ascher, DB ; Farrar, J ; Khor, CC ; Teo, YY ; Inouye, M ; Caws, M ; Dunstan, SJ (NATURE PUBLISHING GROUP, 2018-06)
    To examine the transmission dynamics of Mycobacterium tuberculosis (Mtb) isolated from tuberculosis patients in Ho Chi Minh City, Vietnam, we sequenced the whole genomes of 1,635 isolates and compared these with 3,144 isolates from elsewhere. The data identify an underlying burden of disease caused by the endemic Mtb lineage 1 associated with the activation of long-term latent infection, and a threefold higher burden associated with the more recently introduced Beijing lineage and lineage 4 Mtb strains. We find that Beijing lineage Mtb is frequently transferred between Vietnam and other countries, and detect higher levels of transmission of Beijing lineage strains within this host population than the endemic lineage 1 Mtb. Screening for parallel evolution of Beijing lineage-associated SNPs in other Mtb lineages as a signal of positive selection, we identify an alteration in the ESX-5 type VII-secreted protein EsxW, which could potentially contribute to the enhanced transmission of Beijing lineage Mtb in Vietnamese and other host populations.