Abstract

This proposal is to allow data collection from crystals with several different inhibitors bound to the T. cruzi HGPRTase. Lead compounds have been identified using bacterial complementation screening protocol developed by collaborators at U. of NC at Chapel Hill. Seven compounds have been identified as having higher inhibitory effect of the T. cruzi HPRTase than they have on the human HPRTase. Of these seven compounds identified to date, four of them have been tested in crystallizatioon experiments and have produced crystals of type #1. this ongoing effort to identify antiparasitic drugs will undoubtedly benefit from having the highest resolution data possible. Since some of the inhibitors only allow the growth of small crystals, synchrotron sources are indispensible to the long term goal of this project.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-20
Application #
6119430
Study Section
Project Start
1999-03-01
Project End
2000-04-14
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
20
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

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

  Publications

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
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
Dods, Robert; Båth, Petra; Arnlund, David et al. (2017) From Macrocrystals to Microcrystals: A Strategy for Membrane Protein Serial Crystallography. Structure 25:1461-1468.e2
de Vries, Robert P; Tzarum, Netanel; Peng, Wenjie et al. (2017) A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors. EMBO Mol Med 9:1314-1325

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