The catalytic pathway of horseradish peroxidase at high resolution

Berglund, G.I.; Carlsson, Gunilla; Smith, Andrew T.; Szöke, H.; Henriksen, A.; Hajdu, János

doi:10.1038/417463a

Cited by 853 publications

(852 citation statements)

References 27 publications

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“…For ferryl the distance from the iron atom to the center of the ligand electron density is 1.9 Å, which is shorter than the normal Fe‐O distance of 2.2–2.3 Å in most aquo‐metHb and metMb structures. The modeled Fe‐O distance of 1.9 Å is consistent with previously reported ferryl complexes in peroxidases 39. The occupancy of water coordinated to the iron atom of metHb may make it less stable.…”

Section: Discussionsupporting

confidence: 88%

Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase‐1

et al. 2016

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Despite advances in our understanding of the oxidative pathways mediated by free hemoglobin (Hb), the precise contribution of its highly reactive redox forms to tissue and organ toxicities remains ambiguous. Heme, a key degradation byproduct of Hb oxidation, has recently been recognized as a damage‐associated molecular pattern (DAMP) molecule, able to trigger inflammatory responses. Equally damaging is the interaction of the highly redox active forms of Hb with other biological molecules. We determined the kinetics of heme loss from individual Hb redox states—ferrous (Fe2+), ferric (Fe3+), and ferryl (Fe4+)—using two different heme receptor proteins: hemopexin (Hxp), a naturally occurring heme scavenger in plasma, and a double mutant (H64Y/V86F), apomyoglobin (ApoMb), which avidly binds heme released from Hb. We show for the first time that ferric Hb (Fe3+) loses heme at rates substantially higher than that of ferryl Hb (Fe4+). This was also supported by a higher expression of heme oxygenase‐1 (HO‐1) when ferric Hb was added to cultured lung alveolar epithelial cells (E10). The reported cytotoxicity of Hb may therefore be attributed to a combination of accelerated heme loss from the ferric form and protein radical formation associated with ferryl Hb. Targeted therapeutic interventions can therefore be designed to curb specific oxidative pathways of Hb in hemolytic anemias and when Hb is used as an oxygen‐carrying therapeutic.

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Section: Discussionsupporting

confidence: 88%

Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase‐1

et al. 2016

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“…The root mean square displacements of the C␣ atoms between the ligand-free and the oxy forms are small and equal to 0.182, 0.190, and 0.163 Å for the three HmuO molecules in the asymmetric unit. In agreement with the resonance Raman results, O 2 binds end-on to the heme iron with a bend angle of ϳ110 o , which is more acute than the bend angle reported for the high resolution crystal structures of oxy forms of Mb (122 o (47). In HmuO, the distance between the terminal oxygen atom of bound O 2 and the porphyrin ␣-meso-carbon atom is ϳ3.4 Å.…”

Section: Resultssupporting

confidence: 70%

Crystal Structure of the Dioxygen-bound Heme Oxygenase from Corynebacterium diphtheriae

Unno

Matsui

Chu

et al. 2004

Journal of Biological Chemistry

100

171

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HmuO, a heme oxygenase of Corynebacterium diphtheriae, catalyzes degradation of heme using the same mechanism as the mammalian enzyme. The oxy form of HmuO, the precursor of the catalytically active ferric hydroperoxo species, has been characterized by ligand binding kinetics, resonance Raman spectroscopy, and x-ray crystallography. The oxygen association and dissociation rate constants are 5 M ؊1 s ؊1 and 0.22 s ؊1 , respectively, yielding an O 2 affinity of 21 M ؊1 , which is ϳ20 times greater than that of mammalian myoglobins. However, the affinity of HmuO for CO is only 3-4-fold greater than that for mammalian myoglobins, implying the presence of strong hydrogen bonding interactions in the distal pocket of

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“…The discrepancy between spectroscopic and crystallographic data prompted us to reexamine the Ni coordination and is explained by the effect of radiation on the oxidation state of Ni. It has been observed that radiation-induced changes of the metal center's oxidation state can take place during exposure to x-rays (26). The reduction of Ni(III) in the resting enzyme during x-ray data collection became evident from a difference Fourier omit map calculated with an initial fraction of data collected in a multiple-wavelength anomalous dispersion experiment (lowdose data set, see Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

Crystal structure of nickel-containing superoxide dismutase reveals another type of active site

Wuerges

Lee

Yim

et al. 2004

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

326

403

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Superoxide dismutases (SODs, EC 1.15.1.1) are ubiquitous enzymes that efficiently catalyze the dismutation of superoxide radical anions to protect biological molecules from oxidative damage. The crystal structure of nickel-containing SOD (NiSOD) from Streptomyces seoulensis was determined for the resting, x-ray-reduced, and thiosulfate-reduced enzyme state. NiSOD is a homohexamer consisting of four-helix-bundle subunits. The catalytic center resides in the N-terminal active-site loop, where a Ni(III) ion is coordinated by the amino group of His-1, the amide group of Cys-2, two thiolate groups of Cys-2 and Cys-6, and the imidazolate of His-1 as axial ligand that is lost in the chemically reduced state as well as after x-ray-induced reduction. This structure represents a third class of SODs concerning the catalytic metal species, subunit structure, and oligomeric organization. It adds a member to the small number of Ni-metalloenzymes and contributes with its Ni(III) active site to the general understanding of Ni-related biochemistry. NiSOD is shown to occur also in bacteria other than Streptomyces and is predicted to be present in some cyanobacteria.

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The catalytic pathway of horseradish peroxidase at high resolution

Cited by 853 publications

References 27 publications

Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase‐1

Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase‐1

Crystal Structure of the Dioxygen-bound Heme Oxygenase from Corynebacterium diphtheriae

Crystal structure of nickel-containing superoxide dismutase reveals another type of active site

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