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. The goal of our research is to apply structural biology and high performance computer simulation to investigate molecular mechanisms of bacterial resistance to mercury. Specifically we are interested in solving the first ever X-ray crystal structure of the metal-responsive transcriptional regulator MerR. MerR is the archetype of the MerR family of metalloregulators that controls the transcription of a set of genes (the mer operon) providing Hg resistance in many genera of bacteria isolated from Hg-exposed ecosystems. The mer operon encodes specific genes that facilitate transport of Hg species cleavage of organomercurials and reduction of ionic Hg(II) to volatile elemental Hg(0). The 144-residue MerR binds to its operator DNA and functions as a homodimer. It represses transcription of the mer operon in the absence of Hg(II) and activates transcription upon Hg(II) binding. We wish to obtain a high resolution model to fully characterize Hg(II) binding to MerR. This structural model of MerR will support ongoing neutron scattering and Molecular Dynamics (MD) experiments aimed at studying MerR dynamics and conformational changes upon Hg(II) binding that are essential for understanding its unique mechanism of transcriptional regulation. It is well-known that these multidisciplinary structural studies require maximal resolution X-ray structures of the protein element. As a result a high flux beamline is required to collect high quality data for this proposed research. One day of beamtime (3 shifts) is requested to complete the proposed diffraction studies. We plan to screen crystals of MerR for X-ray diffraction quality and to collect complete redundant data at the highest resolution possible. Structure determination will then be completed by molecular replacement using either a known structure of a paralogous member of the MerR family or by using our current homology model of MerR.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Chicago
Schools of Medicine
United States
Zip Code
Fournier, Bertrand; Sokolow, Jesse; Coppens, Philip (2016) Analysis of multicrystal pump-probe data sets. II. Scaling of ratio data sets. Acta Crystallogr A Found Adv 72:250-60
Mariette, Céline; Guérin, Laurent; Rabiller, Philippe et al. (2015) The creation of modulated monoclinic aperiodic composites in n-alkane/urea compounds. Z Kristallogr Cryst Mater 230:5-11
Sampath, Sujatha; Yarger, Jeffery L (2015) Structural hysteresis in dragline spider silks induced by supercontraction: An x-ray fiber micro-diffraction study. RSC Adv 5:1462-1473
Weingarten, Adam S; Kazantsev, Roman V; Palmer, Liam C et al. (2015) Supramolecular Packing Controls Hâ‚‚ Photocatalysis in Chromophore Amphiphile Hydrogels. J Am Chem Soc 137:15241-6
Coppens, Philip; Fournier, Bertrand (2015) On the scaling of multicrystal data sets collected at high-intensity X-ray and electron sources. Struct Dyn 2:064101
Pfoh, Roland; Pai, Emil F; Saridakis, Vivian (2015) Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides. Acta Crystallogr D Biol Crystallogr 71:2032-9
Liang, Wenguang G; Ren, Min; Zhao, Fan et al. (2015) Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme. J Mol Biol 427:1345-58
Tucker, Chauncey L; Jones, Justin A; Bringhurst, Heidi N et al. (2014) Mechanical and physical properties of recombinant spider silk films using organic and aqueous solvents. Biomacromolecules 15:3158-70
Albertson, Amy E; Teule, Florence; Weber, Warner et al. (2014) Effects of different post-spin stretching conditions on the mechanical properties of synthetic spider silk fibers. J Mech Behav Biomed Mater 29:225-34
Reddy, Vijay S; Nemerow, Glen R (2014) Reply to Campos: Revised structures of adenovirus cement proteins represent a consensus model for understanding virus assembly and disassembly. Proc Natl Acad Sci U S A 111:E4544-5

Showing the most recent 10 out of 94 publications