This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Trace elements are essential for all living organisms. At the same time in cells the concentration of free metal ions is very low, because free redox-active metals can generate radicals, which can lead to cell damage. Others, such as Ca and Zn are participating in signaling processes. This implies the need for tight regulation. In mammals dysfunction of the regulation causes severe diseases. Bacteria would suffer from similar problems in case of too high or too low metal contents. Given the fact that mammalian and bacterial trace element regulation is based on different protein networks, the bacterial metal regulators have attracted considerable attention as potential drug targets. During the past years we have established our research on bacterial metal regulation. Pathogens, such as M. tuberculosis have to contend with iron sequestration in order to survive in the human body. Iron metabolism is regulated by controlling transcription of genes involved in iron uptake, transport and storage. In M. tuberculosis the ferric uptake regulator A (FurA) is activated by Fe2+ to bind specifically to its target DNA sequence thereby repressing the downstream genes. These genes include in homologous cases virulence factors and several proteins required by the bacterium for iron homeostasis. By x-ray absorption spectroscopy we will determine the metal binding sites of the protein. This allows distinguishing between two structurally and functionally distinct FurAMtb metal binding sites and provides a meticulous description plus a qualitative and quantitative characterization of them. Here we propose x-ray absorption spectroscopy measurements on the Mycobacterium tuberculosis iron uptake regulator FurA to further characterize this important gene product in the absence and presence of a new lead compound. For comparison we will include Fur_AF from Acidithiobacillus ferrooxidans, a Gram-negative bacterium living at pH2 2 in high concentrations of soluble ferrous and ferric iron.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Stanford University
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Remesh, Soumya G; Andreatta, Massimo; Ying, Ge et al. (2017) Unconventional Peptide Presentation by Major Histocompatibility Complex (MHC) Class I Allele HLA-A*02:01: BREAKING CONFINEMENT. J Biol Chem 292:5262-5270
VanderLinden, Ryan T; Hemmis, Casey W; Yao, Tingting et al. (2017) Structure and energetics of pairwise interactions between proteasome subunits RPN2, RPN13, and ubiquitin clarify a substrate recruitment mechanism. J Biol Chem 292:9493-9504
Zhang, Haonan; Qiao, Anna; Yang, Dehua et al. (2017) Structure of the full-length glucagon class B G-protein-coupled receptor. Nature 546:259-264
Niedzialkowska, Ewa; Mruga?a, Beata; Rugor, Agnieszka et al. (2017) Optimization of overexpression of a chaperone protein of steroid C25 dehydrogenase for biochemical and biophysical characterization. Protein Expr Purif 134:47-62
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
Tolbert, William D; Gohain, Neelakshi; Alsahafi, Nirmin et al. (2017) Targeting the Late Stage of HIV-1 Entry for Antibody-Dependent Cellular Cytotoxicity: Structural Basis for Env Epitopes in the C11 Region. Structure 25:1719-1731.e4
Yoon, Chun Hong; DeMirci, Hasan; Sierra, Raymond G et al. (2017) Se-SAD serial femtosecond crystallography datasets from selenobiotinyl-streptavidin. Sci Data 4:170055
Warelow, Thomas P; Pushie, M Jake; Cotelesage, Julien J H et al. (2017) The active site structure and catalytic mechanism of arsenite oxidase. Sci Rep 7:1757
Tzarum, Netanel; de Vries, Robert P; Peng, Wenjie et al. (2017) The 150-Loop Restricts the Host Specificity of Human H10N8 Influenza Virus. Cell Rep 19:235-245
Hettle, Andrew; Fillo, Alexander; Abe, Kento et al. (2017) Properties of a family 56 carbohydrate-binding module and its role in the recognition and hydrolysis of ?-1,3-glucan. J Biol Chem 292:16955-16968

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