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AsIII Selectively Induces a Disorder-to-Order Transition in the Metalloid Binding Region of the AfArsR Protein

Tóth, Annamária ; Sajdik, Kadosa ; Gyurcsik, Béla ; Nafaee, Zeyad H. ; Wéber, Edit ; Kele, Zoltan ; Christensen, Niels Johan ; Schell, Juliana ; Correia, Joao Guilherme and Sigfridsson Clauss, Kajsa G.V. LU , et al. (2024) In Journal of the American Chemical Society 146(25). p.17009-17022
Abstract

Arsenic is highly toxic and a significant threat to human health, but certain bacteria have developed defense mechanisms initiated by AsIII binding to AsIII-sensing proteins of the ArsR family. The transcriptional regulator AfArsR responds to AsIII and SbIII by coordinating the metalloids with three cysteines, located in a short sequence of the same monomer chain. Here, we characterize the binding of AsIII and HgII 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... (More)

Arsenic is highly toxic and a significant threat to human health, but certain bacteria have developed defense mechanisms initiated by AsIII binding to AsIII-sensing proteins of the ArsR family. The transcriptional regulator AfArsR responds to AsIII and SbIII by coordinating the metalloids with three cysteines, located in a short sequence of the same monomer chain. Here, we characterize the binding of AsIII and HgII 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 AsIII changes the peptide structure from a random-coil to a well-defined structure of the complex. A trigonal pyramidal AsS3 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 AsIII recognition and response selectivity of AfArsR. Contrary to this, binding of HgII 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 HgII 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Chemical Society
volume
146
issue
25
pages
14 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:38820242
  • scopus:85195038891
ISSN
0002-7863
DOI
10.1021/jacs.3c11665
language
English
LU publication?
yes
id
607f6637-91f5-4c59-aee3-7c47f1503039
date added to LUP
2024-10-09 13:10:20
date last changed
2025-01-01 21:29:57
@article{607f6637-91f5-4c59-aee3-7c47f1503039,
  abstract     = {{<p>Arsenic is highly toxic and a significant threat to human health, but certain bacteria have developed defense mechanisms initiated by As<sup>III</sup> binding to As<sup>III</sup>-sensing proteins of the ArsR family. The transcriptional regulator AfArsR responds to As<sup>III</sup> and Sb<sup>III</sup> by coordinating the metalloids with three cysteines, located in a short sequence of the same monomer chain. Here, we characterize the binding of As<sup>III</sup> and Hg<sup>II</sup> 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<sup>III</sup> changes the peptide structure from a random-coil to a well-defined structure of the complex. A trigonal pyramidal AsS<sub>3</sub> 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<sup>III</sup> recognition and response selectivity of AfArsR. Contrary to this, binding of Hg<sup>II</sup> 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<sup>II</sup> 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.</p>}},
  author       = {{Tóth, Annamária and Sajdik, Kadosa and Gyurcsik, Béla and Nafaee, Zeyad H. and Wéber, Edit and Kele, Zoltan and Christensen, Niels Johan and Schell, Juliana and Correia, Joao Guilherme and Sigfridsson Clauss, Kajsa G.V. and Pittkowski, Rebecca K. and Thulstrup, Peter Waaben and Hemmingsen, Lars and Jancsó, Attila}},
  issn         = {{0002-7863}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{25}},
  pages        = {{17009--17022}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of the American Chemical Society}},
  title        = {{As<sup>III</sup> Selectively Induces a Disorder-to-Order Transition in the Metalloid Binding Region of the AfArsR Protein}},
  url          = {{http://dx.doi.org/10.1021/jacs.3c11665}},
  doi          = {{10.1021/jacs.3c11665}},
  volume       = {{146}},
  year         = {{2024}},
}