Identification and properties of an oxoferryl structure in myeloperoxidase compound II

Wa, Oertling; Hoogland, H.; Gt, Babcock; Wever, R.

doi:10.1021/bi00415a002

Cited by 48 publications

(18 citation statements)

References 39 publications

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“…Consistent with this interpretation, FeAO in F shows a more substantial H 2 O͞D 2 O frequency shift (24,54) and the oxo oxygen is more readily exchanged with solvent water (23). The hydrogen-bonding change at the FeAO moiety in F relative to P (1998) will affect both the optical properties of the heme chromophore and the vibrational properties of the HisOFe IV AO structure (50,(55)(56)(57)(58) (Table 1). Variation in the basicity of the proximal histidine is also a likely contributor to the optical and vibrational differences between the two intermediates.…”

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confidence: 72%

Dioxygen activation and bond cleavage by mixed-valence cytochrome c oxidase

Proshlyakov

Pressler

Babcock

1998

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

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321

374

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Elucidating the structures of intermediates in the reduction of O 2 to water by cytochrome c oxidase is crucial to understanding both oxygen activation and proton pumping by the enzyme. In the work here, the reaction of O 2 with the mixed-valence enzyme, in which only heme a 3 and Cu B in the binuclear center are reduced, has been followed by time-resolved resonance Raman spectroscopy. The results show that OAO bond cleavage occurs within the first 200 s after reaction initiation; the presence of a uniquely stable FeOOOO(H) peroxy species is not detected. The product of this rapid reaction is a heme a 3 oxoferryl (Fe IV AO) species, which requires that an electron donor in addition to heme a 3 and Cu B must be involved. The available evidence suggests that the additional donor is an amino acid side chain. Recent crystallographic data [Yoshikawa, S., Shinzawa-Itoh, K., Nakashima, R., Yaono, R., Yamashita, E. OOH؊ , and the tyrosyl radical. This mechanism provides molecular structures for two key intermediates that drive the proton pump in oxidase; moreover, it has clear analogies to the proposed OOO bond forming chemistry that occurs during O 2 evolution in photosynthesis.The molecular mechanism of dioxygen activation and reduction by the terminal respiratory enzyme, cytochrome c oxidase (CcO), is accessible because of its unique kinetic properties. Elucidation of this mechanism is of fundamental importance in understanding O 2 chemistry in biological systems and necessary for insight into the function of the protein as a redox-linked proton pump. CcO uses four redox-active metal centers, Cu A , heme a, and the heme a 3 ͞Cu B binuclear center, to sustain mitochondrial electron transport by reducing molecular oxygen to water. This reaction ensures a constant flow of electrons through the respiratory chain and the coupled generation of a proton gradient across the mitochondrial membrane, which is required for ATP synthesis. The oxygen chemistry catalyzed by CcO contributes directly to the build-up of the proton gradient because of its redox-linked proton pumping function (1). Thus, the overall reaction catalyzed by CcO may be written aswhere H in ϩ and H out ϩ indicate protons on the matrix (in) and cytosolic (out) sides of the membrane. Because its reaction kinetics is controlled by its proton-pumping function, unique insights into oxygen activation mechanisms are possible (2, 3).A number of reaction intermediates in dioxygen reduction have been identified recently (3, 4). Nonetheless, the timing and mechanism of the critical OAO bond cleavage process in the heme a 3 ͞Cu B binuclear center and the structure of a key intermediate at the peroxy level are poorly understood. In one model, a heme-peroxy adduct [Fe a3 III OOOO(H)] is uniquely stable (2,3,(5)(6)(7)(8). This model contrasts with peroxidases (9) and catalases (10), in which the peroxy OOO bond is spontaneously cleaved to yield an oxoferryl (Fe IV AO) product and a radical. Recent Raman work on the reaction of CcO with H 2 O 2 provided an alternati...

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confidence: 72%

Dioxygen activation and bond cleavage by mixed-valence cytochrome c oxidase

Proshlyakov

Pressler

Babcock

1998

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

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321

374

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“…However, these compounds can be distinguished by the absorbance ratio A 6 2 5 nm/A456 nm which is 0.20 for compound I1 and 0.52 for compound I11 at neutral pH [22]. At high pH the absorption band shifts to 635 nm and the ratio A635 nm/A456 nm changes to 0.25 for compound 11 [23]. A similar value is calculated from the fairly stable final spectrum at pH 10.2 and shows that compound I1 is formed.…”

Section: Resultsmentioning

confidence: 98%

Reaction of myeloperoxidase with its product HOCI

Floris

Wever

1992

European Journal of Biochemistry

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The reaction of human myeloperoxidase with its product, hypochlorous acid was investigated using both rapid-scan spectrophotometry and the stopped-flow technique. In the reaction of myeloperoxidase with hypochlorous acid a primary compound is found with properties similar to that of compound I and which is converted into compound 11. The primary reaction is strongly pHdependent. At pH 7.2 the reaction is too fast to be measured but at higher pH values it is possible to determine the apparent second-order rate constant. Its value decreases to about 2 x lo7 M-' . s-' at pH 8.3 and to 2.3 (+0.4) x lo6 M -l . s-' at pH 9.2, respectively. The dissociation constant for the formation of the primary compound is 25.7 (f 15.3) pM at pH 9.2 and about 2.5 pM at pH 8.3. The apparent second-order rate constant for the formation of compound I1 is hardly affected by pH and varies between 2 to 5 x lo4 M-' . s-' at pH 10.2 and pH 8.3, respectively.Reaction of myeloperoxidase with hypochlorous acid also resulted in irreversible partial bleaching of the chromophore. Chloride, which is a substrate of the enzyme not only protects myeloperoxidase against bleaching by hypochlorous acid but also competitively inhibits the binding of hypochlorous acid to myeloperoxidase, a process which also has been observed in the reaction with hydrogen peroxide. It is concluded that hypochlorous acid binds at the heme iron to form compound I.Myeloperoxidase (donor :hydrogen peroxide oxidoreductase) is a heme-containing enzyme found in the primary granules of human neutrophils. Because of the unique ability of the enzyme to catalyze the H20z-dependent peroxidation of C1-to HOCI, which is an anti-microbial agent, myeloperoxidase is thought to play an important role in the killing of micro-organisms [I, 21. Several spectroscopically distinguishable forms of myeloperoxidase are known : native enzyme, compounds I, I1 and 111. The first step in the peroxidation of chloride is the reaction of myeloperoxidase with hydrogen peroxide to form compound I [3 -51. Compound I is a short-living intermediate in which the prosthetic group is in an oxidized state which is two oxidation equivalents above the ground state. Compound I is very reactive and able to oxidize chloride to hypochlorous acid. The formation of compound I is a very fast process, the apparent second-order rate constant being 2.3 x lo7 M -' . s- ' [5]. The reaction is pHdependent and its rate is governed by a group which, when protonated, prevents H2O2 from binding to myeloperoxidase. The pK, of this group is 4.3 and it has been suggested that the distal histidine with this pK, governs the binding of H2O2 to the enzyme [5, 61.Chloride is able to inhibit the binding of H z 0 2 to myeloperoxidase competitively [5, 7 -101. This process is governed by the same acid/base equilibrium. However, in contrast to H202, chloride binds to the heme iron when the protonatable group is protonated.Reaction of compound I with reductants, such as D-penicillamine [lf], ferrocytochrome c (121 and also hydrogen peroxide [1...

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“…MPO-II is more stable than MPO-I (36,46,47). A good preparation of MPO-II is obtained by adding a 50-fold excess of H 2 O 2 to pure native enzyme.…”

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Kinetics of Oxidation of Tyrosine and Dityrosine by Myeloperoxidase Compounds I and II

Marquez

Dunford

1995

Journal of Biological Chemistry

245

206

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The oxidation of lipoproteins is considered to play a key role in atherogenesis, and tyrosyl radicals have been implicated in the oxidation reaction. Tyrosyl radicals are generated in a system containing myeloperoxidase, H 2 O 2 , and tyrosine, but details of this enzymecatalyzed reaction have not been explored. We have performed transient spectral and kinetic measurements to study the oxidation of tyrosine by the myeloperoxidase intermediates, compounds I and II, using both sequential mixing and single-mixing stopped-flow techniques. The one-electron reduction of compound I to compound II by tyrosine has a second order rate constant of (

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Identification and properties of an oxoferryl structure in myeloperoxidase compound II

Cited by 48 publications

References 39 publications

Dioxygen activation and bond cleavage by mixed-valence cytochrome c oxidase

Dioxygen activation and bond cleavage by mixed-valence cytochrome c oxidase

Reaction of myeloperoxidase with its product HOCI

Kinetics of Oxidation of Tyrosine and Dityrosine by Myeloperoxidase Compounds I and II

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