Workshop on treatment of and postexposure prophylaxis for Burkholderia pseudomallei and B. mallei Infection, 2010.

The US Public Health Emergency Medical Countermeasures Enterprise convened subject matter experts at the 2010 HHS Burkholderia Workshop to develop consensus recommendations for postexposure prophylaxis against and treatment for Burkholderia pseudomallei and B. mallei infections, which cause melioidosis and glanders, respectively. Drugs recommended by consensus of the participants are ceftazidime or meropenem for initial intensive therapy, and trimethoprim/sulfamethoxazole or amoxicillin/clavulanic acid for eradication therapy.

Residual dipolar couplings in NMR structure analysis.

Residual dipolar couplings (RDCs) have recently emerged as a new tool in nuclear magnetic resonance (NMR) with which to study macromolecular structure and function in a solution environment. RDCs are complementary to the more conventional use of NOEs to provide structural information. While NOEs are local-distance restraints, RDCs provide long-range orientational information.

Specific non-native hydrophobic interactions in a hidden folding intermediate: implications for protein folding.

Structures of intermediates and transition states in protein folding are usually characterized by amide hydrogen exchange and protein engineering methods and interpreted on the basis of the assumption that they have native-like conformations. We were able to stabilize and determine the high-resolution structure of a partially unfolded intermediate that exists after the rate-limiting step of a four-helix bundle protein, Rd-apocyt b(562), by multidimensional NMR methods. The intermediate has partial native-like secondary structure and backbone topology, consistent with our earlier native state hydrogen exchange results.

15N chemical shift anisotropy in protein structure refinement and comparison with NH residual dipolar couplings.

Recent methods of aligning proteins which were developed in order to measure residual dipolar couplings (RDCs) in solution can also be used for additional applications such as measuring the 15N CSA in the form of chemical shift differences, Deltadelta. A new XPLOR-NIH module has been developed and implemented for NMR structure refinement using the 15N Deltadelta data as restraints. The results of this refinement are shown using the protein Bax.

Hydrogen bonding in high-resolution protein structures: a new method to assess NMR protein geometry.

An analysis of backbone hydrogen bonds has been performed on nine high-resolution protein X-ray crystal structures. Backbone hydrogen-bond geometry is compared in the context of X-ray crystal structure resolution. A strong correlation between the hydrogen-bond distance, R(HO), and the hydrogen-bond angle, theta(NHO), is observed when the X-ray crystal structure resolution is <1.