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Distal-to-proximal NO conversion in hemoproteins: The role of the proximal pocket

Hough, MA and Antonyuk, SV and Barbieri, S and Rustage, N and McKay, AL and Servid, AE and Eady, RR and Andrew, CR and Hasnain, SS (2011) 'Distal-to-proximal NO conversion in hemoproteins: The role of the proximal pocket.' Journal of Molecular Biology, 405 (2). 395 - 409. ISSN 0022-2836

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Abstract

Hemoproteins play central roles in the formation and utilization of nitric oxide (NO) in cellular signaling, as well as in protection against nitrosative stress. Key to heme-nitrosyl function and reactivity is the Fe coordination number (5 or 6). For (five-coordinate) 5c-NO complexes, the potential for NO to bind on either heme face exists, as in the microbial cytochrome c′ from Alcaligenes xylosoxidans (AxCYTcp), which forms a stable proximal 5c-NO complex via a distal six-coordinate NO intermediate and a putative dinitrosyl species. Strong parallels between the NO-binding kinetics of AxCYTcp, the eukaryotic NO sensor soluble guanylate cyclase, and the ferrocytochrome c/cardiolipin complex have led to the suggestion that a distal-to-proximal NO switch could contribute to the selective ligand responses in gas-sensing hemoproteins. The proximal NO-binding site in AxCYTcp is close to a conserved basic (Arg124) residue that is postulated to modulate NO reactivity. We have replaced Arg124 by five different amino acids and have determined high-resolution (1.07-1.40 Å) crystallographic structures with and without NO. These, together with kinetic and resonance Raman data, provide new insights into the mechanism of distal-to-proximal heme-NO conversion, including the determinants of Fe-His bond scission. The Arg124Ala variant allowed us to determine the structure of an analog of the previously unobserved key 5c-NO distal intermediate species. The very high resolution structures combined with the extensive spectroscopic and kinetic data have allowed us to provide a fresh insight into heme reactivity towards NO, a reaction that is of wide importance in biology. © 2010 Elsevier Ltd. All rights reserved.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Admin
Date Deposited: 04 Aug 2011 15:27
Last Modified: 30 Jan 2019 16:22
URI: http://repository.essex.ac.uk/id/eprint/374

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