Lactoperoxidase haem, an iron-porphyrin thiol.
Ontology highlight
ABSTRACT:
SUBMITTER: Nichol AW
PROVIDER: S-EPMC1148381 | biostudies-other | 1987 Oct
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Cyanide is a well known potent inhibitor of haem proteins, including haem oxygenase (HO). Generally, cyanide coordinates to the ferric haem iron with a linear binding geometry; the Fe-C-N angle ranges from 160 to 180 degrees . The Fe-C-N angle observed in the crystal structure of haem-HO bound to cyanide prepared at alkaline pH was 166 degrees . Here, it is reported that cyanide can bind to the haem iron in HO in a bent mode when the ternary complex is prepared at neutral pH; a crystal structure showed that the Fe-C-N angle was bent by 47 degrees . Unlike the ternary complex prepared at alkaline pH, in which the haem group, including the proximal ligand and the distal helix, was displaced upon cyanide binding, the positions of the haem group and the distal helix in the complex prepared at neutral pH were nearly identical to those in haem-HO. Cyanide that was bound to haem-HO with a bent geometry was readily photodissociated, whereas that bound with a linear geometry was not photodissociated. Thus, alternative cyanide-binding modes with linear and bent geometries exist in the crystalline state of haem-HO.
| S-EPMC2335079 | biostudies-literature
Project description:The coupling of two nitric oxide (NO) molecules in heme active sites is an important contributor to the conversion of NO to nitrous oxide (N(2)O) by heme-containing enzymes. Several formulations for the presumed heme-Fe{N(2)O(2)}(n-) intermediates have been proposed previously, however, no crystal structures of heme-Fe{N(2)O(2)}(n-) systems have been reported to date. We report the first isolation and characterization of a stable bimetallic hyponitrite iron porphyrin, [(OEP)Fe](2)(mu-N(2)O(2)), prepared from the reaction of [(OEP)Fe](2)(mu-O) with hyponitrous acid. Density functional theoretical calculations were performed on the model compound [(porphine)Fe](2)(mu-N(2)O(2)) to characterize its electronic structure and properties.
| S-EPMC2676163 | biostudies-literature
Project description:Iron is an essential element for diverse biological functions. In mammals, the majority of iron is enclosed within a single prosthetic group: heme. In metazoans, heme is synthesized via a highly conserved and coordinated pathway within the mitochondria. However, iron is acquired from the environment and subsequently assimilated into various cellular pathways, including heme synthesis. Both iron and heme are toxic but essential cofactors. How is iron transported from the extracellular milieu to the mitochondria? How are heme and heme intermediates coordinated with iron transport? Although recent studies have answered some questions, several pieces of this intriguing puzzle remain unsolved.
| S-EPMC2930673 | biostudies-literature
Project description:Facultative phototrophs such as Rhodobacter sphaeroides can switch between heterotrophic and photosynthetic growth. This transition is governed by oxygen tension and involves the large-scale production of bacteriochlorophyll, which shares a biosynthetic pathway with haem up to protoporphyrin IX. Here, the pathways diverge with the insertion of Fe2+ or Mg2+ into protoporphyrin by ferrochelatase or magnesium chelatase, respectively. Tight regulation of this branchpoint is essential, but the mechanisms for switching between respiratory and photosynthetic growth are poorly understood. We show that PufQ governs the haem/bacteriochlorophyll switch; pufQ is found within the oxygen-regulated pufQBALMX operon encoding the reaction centre-light-harvesting photosystem complex. A pufQ deletion strain synthesises low levels of bacteriochlorophyll and accumulates the biosynthetic precursor coproporphyrinogen III; a suppressor mutant of this strain harbours a mutation in the hemH gene encoding ferrochelatase, substantially reducing ferrochelatase activity and increasing cellular bacteriochlorophyll levels. FLAG-immunoprecipitation experiments retrieve a ferrochelatase-PufQ-carotenoid complex, proposed to regulate the haem/bacteriochlorophyll branchpoint by directing porphyrin flux toward bacteriochlorophyll production under oxygen-limiting conditions. The co-location of pufQ and the photosystem genes in the same operon ensures that switching of tetrapyrrole metabolism toward bacteriochlorophyll is coordinated with the production of reaction centre and light-harvesting polypeptides.
| S-EPMC5725709 | biostudies-literature
Project description:PurposeThere is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have investigated the effect of quercetin on duodenal non-haem iron absorption in vivo, as well as its effect on factors known to be involved in systemic iron metabolism.MethodsRats were subject to gastric gavage and systemic quercetin administration. Treatments were followed with uptake studies using radiolabeled iron, serum iron and transferrin saturation measurements, LC-MS/MS analysis of quercetin metabolites in serum, determination of tissue non-haem iron content and analysis of gene expression of iron-related proteins.ResultsBoth oral and intraperitoneal (IP) quercetin caused serum and tissue iron depletion by two means, first by increasing mucosal iron uptake and inhibiting iron efflux from duodenal mucosa, and second by decreasing levels of duodenal DMT1, Dcytb and FPN. Additionally, IP quercetin induced highly significant increased liver expression of hepcidin, a hormone known to inhibit intestinal iron uptake.ConclusionsOral quercetin significantly inhibited iron absorption, while IP quercetin significantly affected iron-related genes. These results could lead to development of new effective ways of preventing and treating iron deficiency anaemia, the most widespread nutritional disorder in the world.
| S-EPMC6437293 | biostudies-literature
Project description:The Irr protein from the bacterium Bradyrhizobium japonicum is expressed under iron limitation to mediate iron control of haem biosynthesis. The regulatory input to Irr is the status of haem and its precursors iron and protoporphyrin at the site of haem synthesis. Here, we show that Irr controls the expression of iron transport genes and many other iron-regulated genes not directly involved in haem synthesis. Irr is both a positive and negative effector of gene expression, and in at least some cases the control is direct. Loss of normal iron responsiveness of those genes in an irr mutant, as well as a lower total cellular iron content, suggests that Irr is required for the correct perception of the cellular iron status. Degradation of Irr in iron replete cells requires haem. Accordingly, control of Irr-regulated genes by iron was aberrant in a haem-defective strain, and iron replete mutant cells behave as if they are iron-limited. In addition, the haem mutant had an abnormally high cellular iron content. The findings indicate that B. japonicum senses iron via the status of haem biosynthesis in an Irr-dependent manner to regulate iron homeostasis and metabolism.
| S-EPMC1424673 | biostudies-literature
Project description:Alkyl isonitriles, R-NC, have previously been shown to ligate the heme (haem) iron of cytochromes P450 in both accessible oxidation states (ferrous, Fe2+, and ferric, Fe3+). Herein, the preparation of four steroid-derived isonitriles and their interactions with several P450s, including the steroidogenic CYP17A1 and CYP106A2, as well as the more promiscuous drug metabolizers CYP3A4 and CYP2D6, is described. It was found that successful ligation of the heme iron by the isonitrile functionality for a given P450 depends on both the position and stereochemistry of the isonitrile on the steroid skeleton. Spectral studies indicate that isonitrile ligation of the ferric heme is stable upon reduction to the ferrous form, with reoxidation resulting in the original complex. A crystallographic structure of CYP17A1 with an isonitrile derived from pregnanalone further confirmed the interaction and identified the absolute stereochemistry of the bound species.
| S-EPMC10475101 | biostudies-literature
Project description:The synthesis and spectroscopic characterization of three five-coordinate nitrosyliron(II) complexes, [Fe(Porph)(NO)], are reported. These three nitrosyl derivatives, where Porph represents protoporphyrin IX dimethyl ester, mesoporphyrin IX dimethyl ester, or deuteroporphyrin IX dimethyl ester, display notable differences in their properties relative to the symmetrical synthetic porphyrins such as OEP and TPP. The N-O stretching frequencies are in the range of 1651-1660 cm(-1), frequencies that are lower than those of synthetic porphyrin derivatives. Mössbauer spectra obtained in both zero and applied magnetic field show that the quadrupole splitting values are slightly larger than those of known synthetic porphyrins. The electronic structures of these naturally occurring porphyrin derivatives are thus seen to be consistently different from those of the synthetic derivatives, the presumed consequence of the asymmetric peripheral substituent pattern. The molecular structure of [Fe(PPIX-DME)(NO)] has been determined by X-ray crystallography. Although disorder of the axial nitrosyl ligand limits the structural quality, this derivative appears to show the same subtle structural features as previously characterized five-coordinate nitrosyls.
| S-EPMC3993899 | biostudies-literature
Project description:1. The preparation of a crude extract of Clostridium tetanomorphum containing cobalt porphyrin synthase but little haem-synthase activity is described. 2. The properties of cobalt porphyrin synthase in the clostridial extracts is compared with the properties of a haem synthase present in crude extracts of the yeast Torulopsis utilis. 3. Cobalt porphyrin synthase in extracts of C. tetanomorphum inserts Co(2+) ions into the following dicarboxylic porphyrins in descending order of rate of insertion: meso-, deutero- and proto-porphyrins. Esterification renders meso- and deutero-porphyrins inactive as substrates. Neither the tetracarboxylic (coproporphyrin III) nor the octacarboxylic (uroporphyrin III) compounds are converted into cobalt porphyrins by the extract, but the non-enzymic incorporation of Co(2+) ions into these two porphyrins is rapid. These extracts are unable to insert Mn(2+), Zn(2+), Mg(2+) or Cu(2+) ions into mesoporphyrin. 4. Crude extracts of T. utilis readily insert both Co(2+) and Fe(2+) ions into deutero-, meso, and proto-porphyrins. Unlike the extracts of C. tetanomorphum, these preparations catalyse the insertion of Co(2+) ions into deuteroporphyrin more rapidly than into mesoporphyrin. This parallels the formation of haems by the T. utilis extract. 5. Cobalt porphyrin synthase is present in the particulate fraction of the extracts of C. tetanomorphum but requires a heat-stable factor present in the soluble fraction. This soluble factor can be replaced by GSH. 6. Cobalt porphyrin synthase in the clostridial extract is inhibited by iodoacetamide and to a smaller extent by p-chloromercuribenzoate and N-ethylmaleimide. The haem synthases of T. utilis and Micrococcus denitrificans are also inhibited by various thiol reagents.
| S-EPMC1206588 | biostudies-other
Project description:Oxygen-containing mononuclear iron species--iron(III)-peroxo, iron(III)-hydroperoxo and iron(IV)-oxo--are key intermediates in the catalytic activation of dioxygen by iron-containing metalloenzymes. It has been difficult to generate synthetic analogues of these three active iron-oxygen species in identical host complexes, which is necessary to elucidate changes to the structure of the iron centre during catalysis and the factors that control their chemical reactivities with substrates. Here we report the high-resolution crystal structure of a mononuclear non-haem side-on iron(III)-peroxo complex, [Fe(III)(TMC)(OO)](+). We also report a series of chemical reactions in which this iron(III)-peroxo complex is cleanly converted to the iron(III)-hydroperoxo complex, [Fe(III)(TMC)(OOH)](2+), via a short-lived intermediate on protonation. This iron(III)-hydroperoxo complex then cleanly converts to the ferryl complex, [Fe(IV)(TMC)(O)](2+), via homolytic O-O bond cleavage of the iron(III)-hydroperoxo species. All three of these iron species--the three most biologically relevant iron-oxygen intermediates--have been spectroscopically characterized; we note that they have been obtained using a simple macrocyclic ligand. We have performed relative reactivity studies on these three iron species which reveal that the iron(III)-hydroperoxo complex is the most reactive of the three in the deformylation of aldehydes and that it has a similar reactivity to the iron(IV)-oxo complex in C-H bond activation of alkylaromatics. These reactivity results demonstrate that iron(III)-hydroperoxo species are viable oxidants in both nucleophilic and electrophilic reactions by iron-containing enzymes.
| S-EPMC3306242 | biostudies-literature