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Issue 26, 2012
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Is histidine dissociation a critical component of the NO/H-NOX signaling mechanism? Insights from X-ray absorption spectroscopy

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Abstract

The H-NOX (Heme–Nitric oxide/OXygen binding) family of diatomic gas sensing hemoproteins has attracted great interest. Soluble guanylate cyclase (sGC), the well-characterized eukaryotic nitric oxide (NO) sensor is an H-NOX family member. When NO binds sGC at the ferrous histidine-ligated protoporphyrin-IX, the proximal histidine ligand dissociates, resulting in a 5-coordinate (5c) complex; formation of this 5c complex is viewed as necessary for activation of sGC. Characterization of other H-NOX family members has revealed that while most also bind NO in a 5c complex, some bind NO in a 6-coordinate (6c) complex or as a 5c/6c mixture. To gain insight into the heme pocket structural differences between 5c and 6c Fe(II)–NO H-NOX complexes, we investigated the extended X-ray absorption fine structure (EXAFS) of the Fe(II)–unligated and Fe(II)–NO complexes of H-NOX domains from three species, Thermoanaerobacter tengcongensis, Shewanella woodyi, and Pseudoalteromonas atlantica. Although the Fe(II)–NO complex of TtH-NOX is formally 6c, we found the Fe–NHis bond is substantially lengthened. Furthermore, although NO binds to SwH-NOX and PaH-NOX as a 5c complex, consistent with histidine dissociation, the EXAFS data do not exclude a very weakly associated histidine. Regardless of coordination number, upon NO-binding, the Fe–Nporphyrin bond lengths in all three H-NOXs contract by ∼0.07 Å. This study reveals that the overall heme structure of 5c and 6c Fe(II)–NO H-NOX complexes are substantially similar, suggesting that formal histidine dissociation may not be required to trigger NO/H-NOX signal transduction. The study has refined our understanding of the molecular mechanisms underlying NO/H-NOX signaling.

Graphical abstract: Is histidine dissociation a critical component of the NO/H-NOX signaling mechanism? Insights from X-ray absorption spectroscopy

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Supplementary files

Article information


Submitted
19 Jan 2012
Accepted
14 Feb 2012
First published
17 Feb 2012

Dalton Trans., 2012,41, 7984-7993
Article type
Paper

Is histidine dissociation a critical component of the NO/H-NOX signaling mechanism? Insights from X-ray absorption spectroscopy

Z. Dai, E. R. Farquhar, D. P. Arora and E. M. Boon, Dalton Trans., 2012, 41, 7984
DOI: 10.1039/C2DT30147D

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