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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Scott, Robert A. Cosper, Nathaniel J. Giedroc, David P. Shokes, Jacob E. Pennella, Mario A. |
| Description | Author Affiliation: Pennella MA ( Department of Biochemistry and Biophysics, Center for Advanced Biomolecular Research, Texas A&M University, College Station, TX 77843-2128, USA.); |
| Abstract | Staphylococcus aureus CzrA and Mycobacterium tuberculosis NmtR are homologous zinccobalt-responsive and nickelcobalt-responsive transcriptional repressors in vivo, respectively, and members of the ArsRSmtB superfamily of prokaryotic metal sensor proteins. We show here that Zn(II) is the most potent negative allosteric regulator of czr operatorpromoter binding in vitro with the trend Zn(II)>Co(II)Ni(II), whereas the opposite holds for the binding of NmtR to the nmt operatorpromoter, Ni(II)>Co(II)>Zn(II). Characterization of the metal coordination complexes of CzrA and NmtR by UVvisible and x-ray absorption spectroscopies reveals that metals that form four-coordinate tetrahedral complexes with CzrA [Zn(II) and Co(II)] are potent regulators of DNA binding, whereas metals that form five- or six-coordinate complexes with NmtR [Ni(II) and Co(II)] are the strongest allosteric regulators in this system. Strikingly, the Zn(II) coordination complexes of CzrA and NmtR cannot be distinguished from one another by x-ray absorption spectroscopy, with the best fit a His-3-carboxylate complex in both cases. Inspection of the primary structures of CzrA and NmtR, coupled with previous functional data, suggests that three conserved His and one Asp from the C-terminal alpha5 helix donate ligands to create a four-coordinate complex in both CzrA and NmtR, with NmtR uniquely capable of expanding its coordination number in the Ni(II) and Co(II) complexes by recruiting additional His ligands from a C-terminal extension of the alpha5 helix. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 100 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2003-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Bacterial Proteins Chemistry Metabolism DNA-Binding Proteins Amino Acid Sequence Cobalt Cyanobacteria Genetics Molecular Sequence Data Mycobacterium Tuberculosis Nickel Recombinant Proteins Sequence Alignment Sequence Homology, Amino Acid Spectrophotometry Spectrophotometry, Atomic Staphylococcus Aureus Ultracentrifugation Zinc Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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