The prosthetic group of myeloperoxidase

Wu, N.C.; Schultz, Julius

doi:10.1016/0014-5793(75)80437-6

Cited by 21 publications

(9 citation statements)

References 9 publications

(7 reference statements)

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“…Under these conditions, the formyl side chain of Spirographis heme does not react with cyanide to form a cyanohydrin. Interestingly, UV-visible absorption [Am (e&M): 435 (83), 559 (12), and 596 (10) for Spirographis Mb and 438 (77), 559 (11), and 599 (13) for MPO] and MCD (Fig. 4B) spectral band positions for these Spirographis Mb-and MPO-derived species are nearly identical.…”

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confidence: 78%

“…In addition to this unusual catalytic function, MPO has unique spectroscopic properties with atypically red-shifted UV-visible absorption bands (resulting in its green color) compared to the ordinary heme proteins having the heme b (protoheme IX) or heme c prosthetic group. Despite extensive spectroscopic studies of MPO (3)(4)(5)(6)(7)(8)(9)(10), the chemical structure of the heme-type prosthetic group has not been identified because it is not readily extractable by ordinary methods (11)(12)(13). Two conflicting proposals for the structure have been made: (i) an iron porphyrin with a formyl (electron-withdrawing) peripheral macrocycle substituent(s) such as is present in heme a (14) or (ii) an iron chlorin (dihydroporphyrin) (4)(5)(6)(7)15).…”

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confidence: 99%

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Evidence that a formyl-substituted iron porphyrin is the prosthetic group of myeloperoxidase: magnetic circular dichroism similarity of the peroxidase to Spirographis heme-reconstituted myoglobin.

Sono

Bracete

Huff

et al. 1991

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

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To probe the identity of the active site hemetype prooshetic group ofmyeloperoxidase, whose (5,6,9,10), the spectroscopic properties of analogous derivatives with the same oxidation and ligation states can be used to probe the similarity or difference in their prosthetic group structures. MCD spectral comparison between myoglobin reconstituted with Spirographis heme (Spirographis Mb) and MPO in this study reveals considerable spectral similarities between parallel derivatives of these two proteins, especially in the ferric high-spin native form and the ferrous low-spin complexes. Given the repeatedly demonstrated ability of MCD spectroscopy to identify or distinguish two apparently similar chromophores more definitively than electronic absorption spectroscopy (18-20), the present finding provides strong support for a formyl-substituted porphyrin as the structure of the prosthetic group macrocycle of MPO. EXPERIMENTAL PROCEDURES Spirographis Mb was prepared from horse heart apo-Mb and Spirographis heme as described by Sono and Asakura (16,21,22). MPO was purified from bovine spleen as described (23). Metal-free trans-octaethylchlorin (GEC) was obtained by a published method (24) and metallated to produce Fe-(OEC)Cl using a modification (25) of the direct iron insertion method (26). All chemicals were reagent grade and were obtained from Aldrich or Sigma. N-Methylimidazole and benzene were further purified by distillation.The reduced pyridine hemochromogen [the ferrous bis(pyridine) adduct] of Spirographis heme (and Mb) or MPO was generated by dissolving the heme or diluting the concentrated protein stock solution into a pyridine/NaOH solution [25-35% pyridine (vol/vol) and 0

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confidence: 78%

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confidence: 99%

Evidence that a formyl-substituted iron porphyrin is the prosthetic group of myeloperoxidase: magnetic circular dichroism similarity of the peroxidase to Spirographis heme-reconstituted myoglobin.

Sono

Bracete

Huff

et al. 1991

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

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confidence: 99%

“…Attempts to identify the iron-containing chromophores have been frustrated by their chemical instability (Harrison & Schultz, 1978; Wu & Schultz, 1975;Nichol et al, 1969; Odajima & Yamazaki, 1972b;Newton et al, 1965a,b). The prosthetic groups are covalently linked to the protein (Wu & Schultz, 1975;Schultz et al, 1983). Under conditions examined thus far, cleavage has led to isolation of hemes with physical properties that are distinctly altered from the native enzyme (Harrison & Schultz, 1978;Wu & Schultz, 1975;Nichol et al, 1969).…”

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confidence: 99%

“…The prosthetic groups are covalently linked to the protein (Wu & Schultz, 1975;Schultz et al, 1983). Under conditions examined thus far, cleavage has led to isolation of hemes with physical properties that are distinctly altered from the native enzyme (Harrison & Schultz, 1978;Wu & Schultz, 1975;Nichol et al, 1969). Structural identification has therefore relied principally upon inference from physical characteristics of the intact enzyme.…”

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Structural analysis of myeloperoxidase by resonance Raman spectroscopy

Sibbett¹,

Hurst²

1984

Biochemistry

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Soret excitation of canine myeloperoxidase (MPO) gives rise to a complex resonance Raman (RR) spectrum characterized by multiple bands in the core size and oxidation state marker regions. Relative intensities of the bands obtained by 406- and 454-nm laser excitation were nearly identical and were temperature independent from 77 to 273 K. Spectra of dithionite-reduced and cyanide-coordinated derivatives are also reported. In the native and dithionite-reduced enzyme, there are no detectable bands between 1620 and 1700 cm-1, indicating that the hemes do not contain formyl substituents in conjugation with the macrocyclic ring. Excitation of the visible absorption band at 568 nm gave rise to only very weakly resonance-enhanced spectra. The RR spectra are interpreted within the context of other physical measurements to indicate that MPO contains two equivalent or nearly equivalent chlorin prosthetic groups. Possible mechanistic consequences of these structural features are discussed.

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Hemes, Chlorophylls, and Related Compounds: Biosynthesis and Metabolic Regulation

Granick¹,

Beale²

1978

Advances in Enzymology - And Related Areas of Molecular Biology

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The prosthetic group of myeloperoxidase

Cited by 21 publications

References 9 publications

Evidence that a formyl-substituted iron porphyrin is the prosthetic group of myeloperoxidase: magnetic circular dichroism similarity of the peroxidase to Spirographis heme-reconstituted myoglobin.

Evidence that a formyl-substituted iron porphyrin is the prosthetic group of myeloperoxidase: magnetic circular dichroism similarity of the peroxidase to Spirographis heme-reconstituted myoglobin.

Structural analysis of myeloperoxidase by resonance Raman spectroscopy

Hemes, Chlorophylls, and Related Compounds: Biosynthesis and Metabolic Regulation

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