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| 2. |
- Paul, Jan, et al.
(författare)
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Heme transfer reactions : an important prerequisite for synthetic oxygen carriers
- 1998
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Ingår i: Turkish journal of chemistry. - 1300-0527 .- 1303-6130. ; 22:2, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- Electronic changes of iron- and metal free porphyrins are reviewed in light of their importance to modify the ferri/ferro reduction potential and energy dissipation between ligated carbon monoxide and the porphyrin chelate. Substitutions at positions 2 and 4 are effective ways to exercise this influence. Other measures include exposure to water and modifications of axial ligation, including the \lq three-ligand' case. These measures will also influence the stability of recombined hemin-protein entities, as apparent from the kinetics of heme-transfer from a modified donor protein to apomyoglobin, but the stability appears to be related to the bulkiness of 2,4-substitutional groups rather than to electron availability. It is suggested that the altered stability is a secondary effect from enhanced exposure to water in the crevice.
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| 3. |
- Singh, Amit K, et al.
(författare)
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Bovine Carbonyl Lactoperoxidase Structure at 2.0Å Resolution and Infrared Spectra as a Function of pH.
- 2012
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Ingår i: The protein journal. - : Springer Science and Business Media LLC. - 1875-8355 .- 1572-3887. ; 31:7, s. 598-608
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Tidskriftsartikel (refereegranskat)abstract
- Lactoperoxidase (LPO) is a hemeprotein catalyzing the oxidation of thiocyanate and I(-) into antimicrobials and small aromatic organics after being itself oxidized by H(2)O(2). LPO is excreted by the lungs, mammary glands, found in saliva and tears and protects mammals against bacterial, fungal and viral invasion. The Fe(II) form binds CO which inactivates LPO like many other hemeproteins. We present the 3-dimensional structure of CO-LPO at 2.0Å resolution and infrared (IR) spectra of the iron-bound CO stretch from pH 3 to 8.8 at 1 cm(-1) resolution. The observed Fe-C-O bond angle of 132° is more acute than the electronically related Fe(III), CN-LPO with a Fe-C-N angle of 161°. The orientations of the two ligands are different with the oxygen of CO pointing towards the imidazole of distal His109 while the nitrogen of CN points away, the Fe(II) moves towards His109 while the Fe(III) moves away; both movements are consistent with a hydrogen bond between the distal His109 and CO, but not to the nitrogen of CN-LPO. The IR spectra of CO-LPO exhibit two major CO absorbances with pH dependent relative intensities. Both crystallographic and IR data suggest proton donation to the CO oxygen by His109 with a pK ≈ 4; close to the pH of greatest enzyme turnover. The IR absorbance maxima are consistent with a first order correlation between frequency and Fe(III)/Fe(II) reduction potential at pH 7; both band widths at half-height correlate with electron density donation from Fe(II) to CO as gauged by the reduction potential.
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| 4. |
- Wilczynska, Malgorzata, et al.
(författare)
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A redox-sensitive loop regulates plasminogen activator inhibitor type 2 (PAI-2) polymerization.
- 2003
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 22:8, s. 1753-1761
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Tidskriftsartikel (refereegranskat)abstract
- Plasminogen activator inhibitor type 2 (PAI-2) is the only wild-type serpin that polymerizes spontaneously under physiological conditions. We show that PAI-2 loses its ability to polymerize following reduction of thiol groups, suggesting that an intramolecular disulfide bond is essential for the polymerization. A novel disulfide bond was identified between C79 (in the CD-loop) and C161 (at the bottom of helix F). Substitution mutants in which this disulfide bond was broken did not polymerize. Reactive center loop peptide insertion experiments and binding of bis-ANS to hydrophobic cavities indicate that the C79-C161 disulfide bond stabilizes PAI-2 in a polymerogenic conformation with an open A-beta-sheet. Elimination of this disulfide bond causes A-beta-sheet closure and abrogates the polymerization. The finding that cytosolic PAI-2 is mostly monomeric, whereas PAI-2 in the secretory pathway is prone to polymerize, suggests that the redox status of the cell could regulate PAI-2 polymerization. Taken together, our data suggest that the CD-loop functions as a redox-sensitive switch that converts PAI-2 between an active stable monomeric and a polymerogenic conformation, which is prone to form inactive polymers.
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