This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. LpxA catalyzes the first step in the synthesis of lipid-A, the addition of an acyl-chain to the sugar donor, UDP-GlcNAc. Lipid-A is a glycolipid that is both a potent endotoxin and a required component of cell walls of gram negative bacteria. The latter requirement makes the enzyme a target for the development of anti-bacterial drugs. The glycolipid product makes the system an appropriate target for technology developed in this Research Resource. In the first phase of this project, we undertook a structural characterization of the interaction geometry of LpxA with the acyl-chain donating protein, acyl-carrier protein (ACP). Characterization using residual dipolar coupling (RDC) data, coupled with known structures for the individual proteins, proved successful despite the large size of the complex (~100 kDa). Results have been reported in the literature (Jain, Raetz, Wycoff, Prestegard, J. Mol. Biol., 343: 1379-1389, 2004). Objectives have now turned to the interaction geometry of LpxA and the sugar donor. These studies will again be based on orientational constraints coming from RDC measurements as developed in the Resource, but will be supplemented with more traditional saturation transfer difference (STD) and transfer NOE (trNOE) measurements.
Showing the most recent 10 out of 245 publications
