Abstract

This project involves characterization of two proteins involved in Hg detoxification, MerR and MerA. MerR is the regulatory protein, controlling expression of the rest of the Mer proteins and MerA is the mecuric ion reductase. These proteins play a key role in bacterial Hg detoxification. We will determine what (if any) affect the binding of MerR to DNA has on the Hg site structure. We will compare the Hg site structure with the structures found when Zn, Cd, and Co are bound at the Hg site, in order to address the question of why other metals, that also bind to MerR, do not stimulate transcription. In addition, we will explore the interactions between metal sites ( i.e., Zn will bind to the Hg-MerR -- does this affect the structure?). Our present data, coupled with the known coordination chemistry of Hg(II), suggests that MerR has a trigonal planar site. We will use polarized experiments to test this proposition and to determine the orientation of the Hg site relative to the DNA. Previous work has shown MerA to have a Hg(cys) 2 structure when saturated with Hg. We will characterize the Hg site as a function of Hg loading and NADPH in order to test the alternating sites hypothesis of MerA function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-17
Application #
5222804
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Vickers, Chelsea; Liu, Feng; Abe, Kento et al. (2018) Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display structural and mechanistic similarities to ?-l-fucosidases from GH29. J Biol Chem 293:18296-18308
Nguyen, Phong T; Lai, Jeffrey Y; Lee, Allen T et al. (2018) Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter. Proc Natl Acad Sci U S A 115:E10596-E10604
Aleman, Fernando; Tzarum, Netanel; Kong, Leopold et al. (2018) Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors. Proc Natl Acad Sci U S A 115:7569-7574
Herrera, Nadia; Maksaev, Grigory; Haswell, Elizabeth S et al. (2018) Elucidating a role for the cytoplasmic domain in the Mycobacterium tuberculosis mechanosensitive channel of large conductance. Sci Rep 8:14566
Lal, Neeraj K; Nagalakshmi, Ugrappa; Hurlburt, Nicholas K et al. (2018) The Receptor-like Cytoplasmic Kinase BIK1 Localizes to the Nucleus and Regulates Defense Hormone Expression during Plant Innate Immunity. Cell Host Microbe 23:485-497.e5
Pluvinage, Benjamin; Grondin, Julie M; Amundsen, Carolyn et al. (2018) Molecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont. Nat Commun 9:1043
Beyerlein, Kenneth R; Jönsson, H Olof; Alonso-Mori, Roberto et al. (2018) Ultrafast nonthermal heating of water initiated by an X-ray Free-Electron Laser. Proc Natl Acad Sci U S A 115:5652-5657
Yoshizawa, Takuya; Ali, Rustam; Jiou, Jenny et al. (2018) Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites. Cell 173:693-705.e22
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
Oberthuer, Dominik; Knoška, Juraj; Wiedorn, Max O et al. (2017) Double-flow focused liquid injector for efficient serial femtosecond crystallography. Sci Rep 7:44628

Showing the most recent 10 out of 604 publications