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. We have collected data and determined the structures of several macromolecules that are important in various ways to human health. We determined the structure of the mouse iodotyrosine dehaogenase (IYD) with and without bound substrates, di-iodotyrosine and mono-iodotyrosine. This structure has important implications for human hypothyroidisms caused by congenital mutations in this protein. We also determined the structure of an M.tuberculosis drug target, a glutamine dependent NAD+ synthetase. This was the first structure of this class of enzymes, and it revealed several features of the enzyme for which there is no precedence. We also determined the structures of the liganded and unliganded forms of Mph(R), an erythromycin-binding bacterial repressor, which will be used for the bioengineering of more specific macrolide sensor molecules.
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