Tam L. Nguyen - Storming Media

Inhibition of Metalloprotease Botulinum Serotype A from a Pseudo-Peptide Binding Mode to a Small Molecule that is Active in Primary Neurons

16 FEB 2007

13 pages

Authors: James C. Burnett; Gordon Ruthel; Christian M. Stegmann; Rekha G. Panchal; Tam L. Nguyen; Ann R. Hermone; Robert G. Stafford; Douglas J. Lane; Tara A. Kenny; Connor F. McGarth; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD

The full text of this report is available for sale.

An efficient research strategy integrating empirically-guided, structure-based modeling and chemoinformatics was used to discover potent small molecule inhibitors of the botulinum neurotoxin serotype A light chain. First, a modeled binding mode for inhibitor 2-mercapto-3-phenylpropionyl-RATKML (K(i) = 330 nM) was generated, and required the use of a molecular dynamic conformer of the enzyme displaying the reorientation of surface loops bordering the substrate binding cleft. These flexible loops are conformationally variable in ...

Anthrax Biosensor, Protective Antigen Ion Channel Asymmetric Blockade

07 OCT 2005

8 pages

Authors: Kelly M. Halverson; Rekha G. Panchal; Tam L. Nguyen; Rick Gussio; Stephen F. Little; Martin Misakian; Sina Bavari; John J. Kasianowicz; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD

Bacillus anthracis secretes three proteins (protective antigen, PA; lethal factor, LF; and edema factor, EF) that are the basis for anthrax infection. We present electrophysiological measurements that demonstrate the effect of full-length LF and EF on ion channels formed by the proteolytically activated species of PA (PA63) in planar lipid bilayer membranes. LF and EF convert the heptameric PA63 channel current-voltage relationship from slightly nonlinear to one that is highly ...

An All-Atom Model of the Pore-Like Structure of Hexameric VP40 from Ebola: Structural Insights into the Monomer-Hexamer Transition

30 APR 2005

12 pages

Authors: Tam L. Nguyen; Guy Schoehn; Winfried Weissenhorn; Ann R. Hermone; James C. Burnett; Rekha G. Panchal; Connor McGrath; Dan W. Zaharevitz; M. J. Aman; Rick Gussio; Sina Bavari; NATIONAL CANCER INST FREDERICK MD

The matrix protein VP40 is an indispensable component of viral assembly and budding by the Ebola virus. VP40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the Ebola viral life cycle. While the X-ray structures of monomeric and octameric VP40 have been determined, the structure of hexameric VP40 has only been solved by three-dimensional electron microscopy (EM) ...