Nitrosylation of nitric-oxide-sensing regulatory proteins containing [4Fe-4S] clusters gives rise to multiple iron-nitrosyl complexes

Pauline N. Serrano, Hongxin Wang, Jason C. Crack, Christopher Prior, Matthew I. Hutchings, Andrew J. Thomson, Saeed Kamali, Yoshitaka Yoda, Jiyong Zhao, Michael Y. Hu , Ercan E. Alp, Vasily S. Oganesyan, Nick E. Le Brun, Stephen P. Cramer

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The reaction of protein-bound iron–sulfur (Fe-S) clusters with nitric oxide (NO) plays key roles in NO-mediated toxicity and signaling. Elucidation of the mechanism of the reaction of NO with DNA regulatory proteins that contain Fe-S clusters has been hampered by a lack of information about the nature of the iron-nitrosyl products formed. Herein, we report nuclear resonance vibrational spectroscopy (NRVS) and density functional theory (DFT) calculations that identify NO reaction products in WhiD and NsrR, regulatory proteins that use a [4Fe-4S] cluster to sense NO. This work reveals that nitrosylation yields multiple products structurally related to Roussin's Red Ester (RRE, [Fe2(NO)4(Cys)2]) and Roussin's Black Salt (RBS, [Fe4(NO)7S3]. In the latter case, the absence of 32S/34S shifts in the Fe−S region of the NRVS spectra suggest that a new species, Roussin's Black Ester (RBE), may be formed, in which one or more of the sulfide ligands is replaced by Cys thiolates.
Original languageEnglish
Pages (from-to)14575–14579
Number of pages5
JournalAngewandte Chemie-International Edition
Issue number47
Early online date25 Oct 2016
Publication statusPublished - 14 Nov 2016


  • gene regulation
  • iron–sulfur clusters
  • nitric oxide
  • nuclear vibrational resonance spectroscopy
  • synchrotron radiation

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