Abstract

The parasitic trypanosomal species of the genera Trypanosoma and Leishmania are the causative agents of a wide variety of severely destructive diseases. One of the deadliest of these diseases is African sleeping sickness, the causative agent of which is Trypanosoma bruccei. Compounds which selectively inhibit trypanosomal glycolytic enzymes over the equivalent human glycolytic enzymes would be an excellent starting point for the design of new drugs effective in attentuating trypanosomal diseases. We propose to employ a cyclic process of three-dimensional structure determination and molecular modelling in the search for such compounds. This proposal concerns the structural determination aspect of the drug design cycle pertaining to two of these trypanosomal glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and aldolase.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-22
Application #
6437453
Study Section
Project Start
2001-03-01
Project End
2002-02-28
Budget Start
Budget End
Support Year
22
Fiscal Year
2001
Total Cost
$143,176
Indirect Cost

  Institution

Name
Stanford University
Department
Type
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Vickers, Chelsea; Liu, Feng; Abe, Kento et al. (2018) Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display structural and mechanistic similarities to ?-l-fucosidases from GH29. J Biol Chem 293:18296-18308
Nguyen, Phong T; Lai, Jeffrey Y; Lee, Allen T et al. (2018) Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter. Proc Natl Acad Sci U S A 115:E10596-E10604
Aleman, Fernando; Tzarum, Netanel; Kong, Leopold et al. (2018) Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors. Proc Natl Acad Sci U S A 115:7569-7574
Herrera, Nadia; Maksaev, Grigory; Haswell, Elizabeth S et al. (2018) Elucidating a role for the cytoplasmic domain in the Mycobacterium tuberculosis mechanosensitive channel of large conductance. Sci Rep 8:14566
Lal, Neeraj K; Nagalakshmi, Ugrappa; Hurlburt, Nicholas K et al. (2018) The Receptor-like Cytoplasmic Kinase BIK1 Localizes to the Nucleus and Regulates Defense Hormone Expression during Plant Innate Immunity. Cell Host Microbe 23:485-497.e5
Pluvinage, Benjamin; Grondin, Julie M; Amundsen, Carolyn et al. (2018) Molecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont. Nat Commun 9:1043
Beyerlein, Kenneth R; Jönsson, H Olof; Alonso-Mori, Roberto et al. (2018) Ultrafast nonthermal heating of water initiated by an X-ray Free-Electron Laser. Proc Natl Acad Sci U S A 115:5652-5657
Yoshizawa, Takuya; Ali, Rustam; Jiou, Jenny et al. (2018) Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites. Cell 173:693-705.e22
Guillaume, Joren; Wang, Jing; Janssens, Jonas et al. (2017) Galactosylsphingamides: new ?-GalCer analogues to probe the F'-pocket of CD1d. Sci Rep 7:4276
Ishigami, Izumi; Zatsepin, Nadia A; Hikita, Masahide et al. (2017) Crystal structure of CO-bound cytochrome c oxidase determined by serial femtosecond X-ray crystallography at room temperature. Proc Natl Acad Sci U S A 114:8011-8016

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