Preparation of mesoporphyrin IX and copper and manganese mesoporphyrin complexes of apohemoglobin

Fabry, Thomas L.; Simo, Constance; Javaherian, Kashi

doi:10.1016/0005-2795(68)90072-x

Cited by 41 publications

(18 citation statements)

References 10 publications

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“…Reconstitution of holoenzyme with non-iron metalloporphyrins has long been used in studies ranging from hemoglobin (40) to prostaglandin H 2 synthase-1 (41). Recently, a novel way of introduction of heme cofactor analogs into proteins at the level of protein expression was presented (42).…”

Section: Discussionmentioning

confidence: 99%

Active Cystathionine β-Synthase Can Be Expressed in Heme-free Systems in the Presence of Metal-substituted Porphyrins or a Chemical Chaperone

Majtán

Singh

Wang

et al. 2008

Journal of Biological Chemistry

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Cystathionine ␤-synthase (CBS), a key enzyme in the metabolism of homocysteine, has previously been shown to require a heme co-factor for maximal activity. However, the biochemical function of the CBS heme is not well defined. Here, we show that expression of human CBS in heme-deficient strains of Saccharomyces cerevisiae and Escherichia coli results in production of an enzyme that is misfolded and degraded. Addition of exogenous heme, porphyrins with non-iron metal, or porphyrin lacking metal entirely produced stable and active CBS enzyme. Purification of recombinant CBS enzyme expressed in the presence of various metalloporphyrins confirmed that Mn(III) and Co(III) had 30 -60% of the specific activity of Fe(III)-CBS, and still responded to allosteric activation by S-adenosyl-L-methionine. Treatment of S. cerevisiae with the chemical chaperone trimethylamine-N-oxide resulted in near complete restoration of function to human CBS produced in a heme-deficient strain. Taken together, these results suggest that porphyrin moiety of the heme plays a critical role in proper CBS folding and assembly, but that the metal ion is not essential for this function or for allosteric regulation by S-adenosyl-L-methionine.

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Section: Discussionmentioning

confidence: 99%

Active Cystathionine β-Synthase Can Be Expressed in Heme-free Systems in the Presence of Metal-substituted Porphyrins or a Chemical Chaperone

Majtán

Singh

Wang

et al. 2008

Journal of Biological Chemistry

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“…In many cases, these Mn-substituted derivatives were investigated in order to provide insight on the role of heme iron in the reactions of the native proteins [12]. Manganesesubstituted derivatives of heme proteins that have been reported to date include those of Hb [13,14], myoglobin (Mb) [15][16][17], cytochrome P450 [18], sGC [19], cytochrome c [20], nitric oxide synthase [21], horseradish peroxidase [14,16,22], cytochrome b 5 [23], CcP [16,24,25], and PGHS-1 [26].…”

Section: Introductionmentioning

confidence: 99%

Crystal structures of manganese- and cobalt-substituted myoglobin in complex with NO and nitrite reveal unusual ligand conformations

Zahran

Chooback

Copeland

et al. 2008

Journal of Inorganic Biochemistry

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Nitrite is now recognized as a storage pool of bioactive nitric oxide (NO). Hemoglobin (Hb) and myoglobin (Mb) convert, under certain conditions, nitrite to NO. This newly discovered nitrite reductase activity of Hb and Mb provides an attractive alternative to mammalian NO synthesis from the NO synthase pathway that requires dioxygen. We recently reported the X-ray crystal structure of the nitrite adduct of ferric horse heart Mb, and showed that the nitrite ligand binds in an unprecedented O-binding (nitrito) mode to the d(5) ferric center in Mb(III)(ONO) [D.M. Copeland, A. Soares, A.H. West, G.B. Richter-Addo, J. Inorg. Biochem. 100 (2006) 1413-1425]. We also showed that the distal pocket in Mb allows for different conformations of the NO ligand (120 degrees and 144 degrees ) in Mb(II)NO depending on the mode of preparation of the compound. In this article, we report the crystal structures of the nitrite and NO adducts of manganese-substituted hh Mb (a d(4) system) and of the nitrite adduct of cobalt-substituted hh Mb (a d(6) system). We show that the distal His64 residue directs the nitrite ligand towards the rare nitrito O-binding mode in Mn(III)Mb and Co(III)Mb. We also report that the distal pocket residues allow a stabilization of an unprecendented bent MnNO moiety in Mn(II)MbNO. These crystal structural data, when combined with the data for the aquo, methanol, and azide MnMb derivatives, provide information on the role of distal pocket residues in the observed binding modes of nitrite and NO ligands to wild-type and metal-substituted Mb.

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“…In the deoxy form of coboglobin, cobalt is low spin rather than high spin and the best estimates from simple cobalt model systems indicate that the proximal imidazole in CoHb moves -0. 4 A upon oxygenation'4,'9,20 as opposed to the 0.6 8, for Hb. The resulting motion of the proximal histidine upon binding 0 2 will therefore only be two-thirds as great.…”

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confidence: 97%

Oxygen binding to cobalt porphyrins

et al. 1978

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The thermodynamic constants of oxygen binding to cobalt "picket fence" porphyrin complexes, mejo-tetra(a,a,a,ao-pivalamidophenyl)porphyrinatocobalt(II)-1 -methylimidazole and 1,2-dimethylimidazole, are reported. In contrast to previously studied cobalt porphyrins, these complexes bind oxygen with the same affinity as cobalt substituted myoglobin and hemoglobin. Solvation effects are discussed as the source of this difference. The use of sterically hindered axial bases as models of T state hemoglobin is discussed.

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Preparation of mesoporphyrin IX and copper and manganese mesoporphyrin complexes of apohemoglobin

Cited by 41 publications

References 10 publications

Active Cystathionine β-Synthase Can Be Expressed in Heme-free Systems in the Presence of Metal-substituted Porphyrins or a Chemical Chaperone

Active Cystathionine β-Synthase Can Be Expressed in Heme-free Systems in the Presence of Metal-substituted Porphyrins or a Chemical Chaperone

Crystal structures of manganese- and cobalt-substituted myoglobin in complex with NO and nitrite reveal unusual ligand conformations

Oxygen binding to cobalt porphyrins

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