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JBIC Journal of Biological Inorganic Chemistry

, Volume 23, Issue 7, pp 1085–1092 | Cite as

Spectroscopic evidence supporting neutral thiol ligation to ferrous heme iron

  • Masanori SonoEmail author
  • Shengfang Sun
  • Anuja Modi
  • Mark S. Hargrove
  • Bastian Molitor
  • Nicole Frankenberg-Dinkel
  • John H. DawsonEmail author
Original Paper
Part of the following topical collections:
  1. Alison Butler: Papers in Celebration of Her 2018 ACS Alfred Bader Award in Bioorganic or Bioinorganic Chemistry

Abstract

The binding of neutral thiol (ethanethiol, EtSH) or thioether (tetrahydrothiophene, THT) to two types of heme proteins in their ferrous state has been investigated with UV–visible (UV–Vis) absorption and magnetic circular dichroism spectroscopy. For the second GAF (cGMP-specific phosphodiesterases, adenylyl cyclases, and FhlA) domain from the sensory kinase MsmS (sGAF2), stepwise additions of these respective two sulfur-donor ligands to its dithionite-reduced ferrous form generate homogeneous six-coordinate low-spin ferrous complexes at both pHs 7.0 and 5.4. Similar complexes were partially formed for deoxyferrous soybean leghemoglobin with EtSH or THT within their solubility limits in water. The titrations cause significant UV–Vis spectra changes attributable to a five-coordinate to six-coordinate heme iron coordination change. For sGAF2, the resulting spectra are essentially identical for the both ligands, clearly indicating the direct binding of neutral thiol/thioether to ferrous heme iron as the distal ligand. On the other hand, the thiol EtSH binds to ferric sGAF2 in the anionic thiolate form, while thioether THT forms its ferric sGAF2 complex as a neutral ligand. These observations provide compelling evidence that neutral cysteine is a plausible ligand for ferrous heme proteins.

Graphical abstract

Keywords

Thiols as heme axial ligands Magnetic circular dichroism spectroscopy Soybean leghemoglobin Sensory kinase MsmS The second GAF domain (sGAF2) 

Notes

Acknowledgements

This work was supported by the National Institutes of Health (GM 26730) and Research Corp. (to J.H.D.).

Supplementary material

775_2018_1611_MOESM1_ESM.pdf (1.3 mb)
Supplementary material 1 (PDF 1328 kb)

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Copyright information

© SBIC 2018

Authors and Affiliations

  • Masanori Sono
    • 1
    Email author
  • Shengfang Sun
    • 1
  • Anuja Modi
    • 1
    • 5
  • Mark S. Hargrove
    • 2
  • Bastian Molitor
    • 3
  • Nicole Frankenberg-Dinkel
    • 4
  • John H. Dawson
    • 1
    Email author
  1. 1.Department of Chemistry and BiochemistryUniversity of South CarolinaColumbiaUSA
  2. 2.Roy J. Carver Department of Biochemistry, Biophysics, and Molecular BiologyIowa State UniversityAmesUSA
  3. 3.Center for Applied GeosciencesUniversity of TübingenTübingenGermany
  4. 4.Technische Universität Kaiserslautern, Fachbereich Biologie, Abt. MikrobiologieKaiserslauternGermany
  5. 5.Center for Alzheimer’s and Neurodegenerative Diseases, UT Southwestern Medical CenterDallasUSA

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