| Autor: |
Tóth A; Department of Molecular and Analytical Chemistry, University of Szeged, Dóm tér 7-8, H-6720 Szeged, Hungary., Sajdik K; Department of Molecular and Analytical Chemistry, University of Szeged, Dóm tér 7-8, H-6720 Szeged, Hungary., Gyurcsik B; Department of Molecular and Analytical Chemistry, University of Szeged, Dóm tér 7-8, H-6720 Szeged, Hungary., Nafaee ZH; Department of Molecular and Analytical Chemistry, University of Szeged, Dóm tér 7-8, H-6720 Szeged, Hungary., Wéber E; Department of Medical Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.; HUN-REN-SZTE Biomimetic Systems Research Group, Dóm tér 8, H-6720 Szeged, Hungary., Kele Z; Department of Medical Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary., Christensen NJ; Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark., Schell J; Institute for Materials Science and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, 45141 Essen, Germany.; European Organization for Nuclear Research (CERN), CH-1211 Geneva, Switzerland., Correia JG; Centro de Cięncias e Tecnologias Nucleares, Departamento de Engenharia e Cięncias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, 2695-066 Bobadela LRS, Portugal.; European Organization for Nuclear Research (CERN), CH-1211 Geneva, Switzerland., Sigfridsson Clauss KGV; MAX IV Laboratory, Lund University, P.O. Box 118, SE-221 00 Lund, Sweden., Pittkowski RK; Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Kobenhavn Ø, Denmark., Thulstrup PW; Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Kobenhavn Ø, Denmark., Hemmingsen L; Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Kobenhavn Ø, Denmark., Jancsó A; Department of Molecular and Analytical Chemistry, University of Szeged, Dóm tér 7-8, H-6720 Szeged, Hungary. |
| Abstrakt: |
Arsenic is highly toxic and a significant threat to human health, but certain bacteria have developed defense mechanisms initiated by As III binding to As III -sensing proteins of the ArsR family. The transcriptional regulator AfArsR responds to As III and Sb III by coordinating the metalloids with three cysteines, located in a short sequence of the same monomer chain. Here, we characterize the binding of As III and Hg II to a model peptide encompassing this fragment of the protein via solution equilibrium and spectroscopic/spectrometric techniques (pH potentiometry, UV, CD, NMR, PAC, EXAFS, and ESI-MS) combined with DFT calculations and MD simulations. Coordination of As III changes the peptide structure from a random-coil to a well-defined structure of the complex. A trigonal pyramidal AsS 3 binding site is formed with almost exactly the same structure as observed in the crystal structure of the native protein, implying that the peptide possesses all of the features required to mimic the As III recognition and response selectivity of AfArsR. Contrary to this, binding of Hg II to the peptide does not lead to a well-defined structure of the peptide, and the atoms near the metal binding site are displaced and reoriented in the Hg II model. Our model study suggests that structural organization of the metal site by the inducer ion is a key element in the mechanism of the metalloid-selective recognition of this protein. |
