Influences of the heme-lysine crosslink in cytochrome P460 over redox catalysis and nitric oxide sensitivity

Ammonia (NH 3 )-oxidizing bacteria (AOB) derive total energy for life from the multi-electron oxidation of NH 3 to nitrite (NO 2 − ). One obligate intermediate of this metabolism is hydroxylamine (NH 2 OH), which can be oxidized to the potent greenhouse agent nitrous oxide (N 2 O) by the AOB enzyme...

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Vydáno v:Chemical science (Cambridge) Ročník 9; číslo 2; s. 368 - 379
Hlavní autoři: Vilbert, Avery C., Caranto, Jonathan D., Lancaster, Kyle M.
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Royal Society of Chemistry 2018
Royal Society of Chemistry (RSC)
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ISSN:2041-6520, 2041-6539
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Shrnutí:Ammonia (NH 3 )-oxidizing bacteria (AOB) derive total energy for life from the multi-electron oxidation of NH 3 to nitrite (NO 2 − ). One obligate intermediate of this metabolism is hydroxylamine (NH 2 OH), which can be oxidized to the potent greenhouse agent nitrous oxide (N 2 O) by the AOB enzyme cytochrome (cyt) P460. We have now spectroscopically characterized a 6-coordinate (6c) {FeNO} 7 intermediate on the NH 2 OH oxidation pathway of cyt P460. This species has two fates: it can either be oxidized to the {FeNO} 6 that then undergoes attack by NH 2 OH to ultimately generate N 2 O, or it can lose its axial His ligand, thus generating a stable, off-pathway 5-coordinate (5c) {FeNO} 7 species. We show that the wild type (WT) cyt P460 exhibits a slow nitric oxide (NO)-independent conversion ( k His-off = 2.90 × 10 −3 s −1 ), whereas a cross-link-deficient Lys70Tyr cyt P460 mutant protein underwent His dissociation via both a NO-independent ( k His-off = 3.8 × 10 −4 s −1 ) and a NO-dependent pathway [ k His-off(NO) = 790 M −1 s −1 ]. Eyring analyses of the NO-independent pathways for these two proteins revealed a significantly larger ( ca. 27 cal mol −1 K −1 ) activation entropy (Δ S ‡ ) in the cross-link-deficient mutant. Our results suggest that the Lys–heme cross-link confers rigidity to the positioning of the heme P460 cofactor to avoid the fast NO-dependent His dissociation pathway and subsequent formation of the off-pathway 5c {FeNO} 7 species. The relevance of these findings to NO signaling proteins such as heme-nitric oxide/oxygen binding (H-NOX) is also discussed.
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AC02-76SF00515; SC0013997
USDOE Office of Science (SC), Basic Energy Sciences (BES)
ISSN:2041-6520
2041-6539
DOI:10.1039/C7SC03450D