1H NMR Study of the Magnetic Properties and Electronic Structure of the Hydroxide Complex of Substrate-bound Heme Oxygenase from Neisseria Meningitidis:  Influence of the Axial Water Deprotonation on the Distal H-bond Network

Ma, Long; Liu, Yangzhong; Zhang, Xuhang; Yoshida, Tadashi; Mar, Gerd N. La

doi:10.1021/ja0584626

Cited by 12 publications

(35 citation statements)

References 61 publications

(241 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 1 H-NMR spectra obtained for IsdIFe 3þ at pH 6, 7, and 8.2 ( Fig. 2A) indicate that the interconversion of coordinated water and coordinated hydroxide is slow on the NMR time scale as previously reported for bovine myoglobin variants in which the distal His is replaced by Gln or Asn (43) and for two bacterial heme oxygenases (41,44).…”

Section: Discussionsupporting

confidence: 75%

Electronic properties of the highly ruffled heme bound to the heme degrading enzyme IsdI

Takayama

Ukpabi

Murphy

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

159

View full text Add to dashboard Cite

IsdI, a heme-degrading protein from Staphylococcus aureus , binds heme in a manner that distorts the normally planar heme prosthetic group to an extent greater than that observed so far for any other heme-binding protein. To understand better the relationship between this distinct structural characteristic and the functional properties of IsdI, spectroscopic, electrochemical, and crystallographic results are reported that provide evidence that this heme ruffling is essential to the catalytic activity of the protein and eliminates the need for the water cluster in the distal heme pocket that is essential for the activity of classical heme oxygenases. The lack of heme orientational disorder in 1 H-NMR spectra of the protein argues that the catalytic formation of β- and δ-biliverdin in nearly equal yield results from the ability of the protein to attack opposite sides of the heme ring rather than from binding of the heme substrate in two alternative orientations.

show abstract

Section: Discussionsupporting

confidence: 75%

Electronic properties of the highly ruffled heme bound to the heme degrading enzyme IsdI

Takayama

Ukpabi

Murphy

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

159

View full text Add to dashboard Cite

show abstract

“…Thus, it can be concluded that in the case of low-spin ferric peroxo/hydroperoxo hemes, the observed EPR spectra with small g spread and 56 The proposal by Rivera was mainly based on the detection of unusual 13 C NMR spectra of the hydroxide complex of HO from Pseudomonas aeroginosa reconstituted with 13 C labeled heme. 55 However, a recent proton NMR investigation of the ferric hydroxide complex of a homologous HO from Neisseria meningitidis has demonstrated unambiguously a d π ground state for the hydroxide complex.…”

Section: Discussion Electronic Structure Analysismentioning

confidence: 99%

Distinct Reaction Pathways Followed upon Reduction of Oxy-Heme Oxygenase and Oxy-Myoglobin as Characterized by Mössbauer Spectroscopy

et al. 2007

View full text Add to dashboard Cite

Activation of O 2 by heme-containing monooxygenases generally commences with the common initial steps of reduction to the ferrous heme and binding of O 2 followed by a one-electron reduction of the O 2 -bound heme. Subsequent steps that generate reactive oxygen intermediates diverge and reflect the effects of protein control on the reaction pathway. In this study, Mössbauer and EPR spectroscopies were used to characterize the electronic states and reaction pathways of reactive oxygen intermediates generated by 77 K radiolytic cryoreduction and subsequent annealing of oxyheme oxygenase (HO) and oxy-myoglobin (Mb). The results confirm that one-electron reduction of (Fe II -O 2 )HO is accompanied by protonation of the bound O 2 to generate a low-spin (Fe III -O 2 H − )HO that undergoes self hydroxylation to form the α-meso-hydroxyhemin-HO product. In contrast, oneelectron reduction of (Fe II -O 2 )Mb yields a low-spin (Fe III -O 2 2− )Mb. Protonation of this intermediate generates (Fe III -O 2 H − )Mb, which then decays to a ferryl complex, (Fe IV =O 2− )Mb, that exhibits magnetic properties characteristic of the compound II species generated in the reactions of peroxide with heme peroxidases and with Mb. Generation of reactive high-valent states with ferryl species via hydroperoxo intermediates is believed to be the key oxygen-activation steps involved in the catalytic cycles of P450-type monooxygenases. The Mössbauer data presented here provide direct spectroscopic evidence supporting the idea that ferric-hydroperoxo hemes are indeed the precursors of the reactive ferryl intermediates. The fact that a ferryl intermediate does not accumulate in HO underscores the determining role played by protein structure in controlling the reactivity of reaction intermediates.

show abstract

“…The chemical shifts for several labile protons in this network exhibit strong low-field bias indicative of significant H-bonding. (23-27)…”

mentioning

confidence: 99%

“…On the one hand, δ dip directly monitors the H-bond properties of the ligated water molecule/hydroxide ion. (26, 27, 31, 33) For high-spin ferrihemoproteins, Δχ is large, negative, highly axial, (26, 31, 34-36) and arises overwhelmingly from the zero-field splitting constant, D, as given by: (32)…”

mentioning

confidence: 99%

Coupling of the Distal Hydrogen Bond Network to the Exogenous Ligand in Substrate-Bound, Resting State Human Heme Oxygenase

et al. 2009

Self Cite

View full text Add to dashboard Cite

Mammalian heme oxygenase, HO, possesses catalytically implicated distal ordered water molecules within an extended H-bond network, with one of the ordered water molecules (#1) providing a bridge between the iron-coordinated ligand and the catalytically critical Asp140, that, in turn, serves as an acceptor for the Tyr58 OH H-bond. The degree of H-bonding by the ligated water molecule and the coupling of this water molecule to the H-bond network are of current interest and are herein investigated by 1 H NMR. 2D NMR allowed sufficient assignments to provide both the H-bond strength and hyperfine shifts, the latter of which were used to quantify the magnetic anisotropy in both the ferric high-spin aquo and low-spin hydroxo complexes. The anisotropy in the aquo complex indicates that the H-bond donation to water #1 is marginally stronger than in a bacterial HO, while the anisotropy for the hydroxo complex reveals a conventional (d xz , d yz ) 1 ground state indicative of only moderate to weak H-bond acceptance by the ligated hydroxide. Mapping out the changes of the H-bond strengths in the network during the ligated water → hydroxide conversion by correcting for the effects of magnetic anisotropy, reveals a very substantial change in H-bond strength for Tyr58 OH, and lesser effects on nearby H-bonds. The effect of pH on the H-bonding network in human HO is much larger and transmitted much further from the iron than in a pathogenic bacterial HO. The implications for the HO mechanism of the H-bond of Tyr58 to Asp140 are discussed. KeywordsMagnetic anisotropy; hyperfine shifts; ligand deprotonation; heme oxygenase; H-bonding Heme oxygenase, HO, 1 is a widely distributed enzyme (1) that uses heme as a substrate and cofactor to cleave the heme via three intermediates, (2-6) as depicted in Figure 1. HOs occur in at least two forms in humans, a constitutive isozyme, designated hHO-2, and an inducible hHO-1. Both are membrane-bound, although the majority of the structure and function ‡ This research was supported by grants from the National Institutes of Health, GM62830 (GNL) and DK30297 (PROM).* lamar@chem.ucdavis.edu; phone: (530) 752-0958; FAX: (530) 752-8995.Supporting Information: Seven Figures (low-field 1 H NMR spectra, aromatic, aliphatic TOCSY, and inter-aliphatic NOESY for hHO-DMDH-H 2 O, and aromatic TOCSY, aromatic NOESY spectra and magnetic axes for hHO-DMDH-OH) and one table of chemical shifts. Total pages, 15. This material is available free of charge via the Internet at http://pubs.acs.org. 1 Abbreviations used: DSS, 2,2-dimethyl-2-silapentane-5-sulfonate; PH, protohemin; DMDH, 2-,4-dimethyldeuterohemin; HO, heme oxygenase, hHO, human heme oxygenase#1; D140A-hHO, Asp140→Ala human heme oxygenase#1; NmHO, Neisseria meningitidis heme oxygenase; CdHO, Corynebacterium diphtheriae heme oxygenase; PaHO, Pseudomonas aeruginosa heme oxygenase; NOESY, two-dimensional nuclear Overhauser spectroscopy; TOCSY, two-dimensional total correlation spectroscopy; NIH Public Access Author ManuscriptBiochemistry. Author ma...

show abstract

¹H NMR Study of the Magnetic Properties and Electronic Structure of the Hydroxide Complex of Substrate-bound Heme Oxygenase from Neisseria Meningitidis: Influence of the Axial Water Deprotonation on the Distal H-bond Network

Cited by 12 publications

References 61 publications

Electronic properties of the highly ruffled heme bound to the heme degrading enzyme IsdI

Electronic properties of the highly ruffled heme bound to the heme degrading enzyme IsdI

Distinct Reaction Pathways Followed upon Reduction of Oxy-Heme Oxygenase and Oxy-Myoglobin as Characterized by Mössbauer Spectroscopy

Coupling of the Distal Hydrogen Bond Network to the Exogenous Ligand in Substrate-Bound, Resting State Human Heme Oxygenase

Contact Info

Product

Resources

About