Biomedical subjects

D E Sayers

Publications and source records attributed to D E Sayers.

23 records · Page 2Linked to original sources

PubMed1986

Structural variations in soluble iron complexes of models for ferritin: an x-ray absorption and Mössbauer spectroscopy comparison of horse spleen ferritin to Blutal (iron-chondroitin sulfate) and Imferon (iron-dextran).

Variations in the turnover of storage iron have been attributed to differences in apoferritin and in the cytoplasm but rarely to differences in the structure of the iron core (except size). To explore the idea that the iron environment in soluble iron complexes could vary, we compared horse spleen ferritin to pharmaceutically important model complexes of hydrous ferric oxide formed from FeCl3 and dextran (Imferon) or chondroitin sulfate (Blutal), using x-ray absorption (EXAFS) and Mössbauer spectroscopy. The results show that the iron in the chondroitin sulfate complex was more ordered than in either horse spleen ferritin or the dextran complex (EXAFS), with two magnetic environments (Mössbauer), one (80%-85%) like Fe2O3 X nH2O (ferritinlike) and one (15%-20%) like Fe2O3 (hematite); since sulfate promotes the formation of inorganic hematite, the sulfate in the chondroitin sulfate most likely nucleated Fe2O3 and hydroxyl/carboxyls, which are ligands common to chondroitin sulfate, ferritin and dextran most likely nucleated Fe2O3 X nH2O. Differences in the structure of the iron complexed with chondroitin sulfate or dextran coincide with altered rates of iron release in vivo and in vitro and provide the first example relating function to local iron structure. Differences might also occur among ferritins in vivo, depending on the apoferritin (variations in anion-binding sites) or the cytoplasm (anion concentration).

Animals↗

PubMed1985

Fe(III).ATP complexes. Models for ferritin and other polynuclear iron complexes with phosphate.

Polynuclear iron complexes of Fe(III) and phosphate occur in seawater and soils and in cells where the iron core of ferritin, the iron storage protein, contains up to 4500 Fe atoms in a complex with an average composition of (FeO.OH)8FeO.OPO3H2. Although phosphate influences the size of the ferritin core and thus the availability of stored iron, little is known about the nature of the Fe(III)-phosphate interaction. In the present study, Fe-phosphate interactions were analyzed in stable complexes of Fe(III).ATP which, in the polynuclear iron form, had phosphate at interior sites. Such Fe(III).ATP complexes are important not only as models but also because they may play a role in intracellular iron transport and in iron toxicity; the complexes were studied by extended x-ray absorption fine structure, EPR, NMR spectroscopy, and measurement of proton release. Mononuclear iron complexes exhibiting a g' = 4.3 EPR signal were formed at Fe:ATP ratios less than or equal to 1:3, and polynuclear iron complexes (Fe greater than or equal to 250, EPR silent at g' = 4.3) were formed at an Fe:ATP ratio of 4:1. No NMR signals due to ATP were observed when Fe was in excess (Fe:ATP = 4:1). Extended x-ray absorption fine structure analysis of the polynuclear Fe(III).ATP complex was able to distinguish an Fe-P distance at 3.27 A in addition to the octahedral O at 1.95 A and 4-5 Fe atoms at 3.36 A. The Fe-O and Fe-Fe distances are the same as in ferritin, and the Fe-P distance is analogous to that in another metal-ATP complex. An observable Fe-P environment in such a large polynuclear iron cluster as the Fe(III).ATP (4:1) complex indicates that the phosphate is distributed throughout rather than merely on the surface, in contrast to earlier models of chelate-stabilized iron clusters. Complexes of Fe(III) and ATP similar to those described here may form in vivo either as normal components of intracellular iron metabolism or during iron excess where the consequent alteration of free nucleotide triphosphate pools could contribute to the observed toxicity of iron.

Adenosine Triphosphate↗

PubMed1983

A distinct environment for iron (III) in the complex with horse spleen apoferritin observed by x-ray absorption spectroscopy.

Cell-specific variations in apoferritin structure correlate with variations in iron metabolism that suggest functional specificity of the protein shell. Using EPR spectroscopy, we previously showed that vanadyl binds to specific sites on apoferritin, and that VO2+ binding is reduced by Fe(II) and Fe(III) (the natural substrates) and by metals known to influence iron storage (Chasteen, N. D., and Theil, E. C. (1982) J. Biol. Chem. 257, 7672-7677). Such observations suggest that the metal-binding site is important to apoferritin function and may define a location where the influence of cell-specific structural features are exerted. To investigate the iron-protein complex further, we have used x-ray absorption spectroscopy and have characterized, for the first time to our knowledge, Fe(III) apparently attached to the protein, after analyzing the x-ray absorption spectrum of an Fe(III)-apoferritin complex (10 Fe/molecule) compared to that of ferritin (polynuclear Fe(III)OOH, about 2000/molecule). The environment of iron in the Fe(III)-protein complex was similar to that in an Fe(III)-oxalate (2:3) hexahydrate complex, both in near edge structure and extended x-ray absorption structure, confirming earlier predictions of carboxylates as protein ligands. The extended x-ray absorption fine structure data for both compounds was fit best by a model in which a second shell of low Z atoms (carbon) was close (0.53-0.55 A) to the first shell of coordinated oxygen. However, small differences between Fe(III)-apoferritin and Fe(III)-oxalate in the Fe-O environment suggest a distorted geometry in the Fe(III)-protein complex and/or the presence of a mixture of atoms, such as nitrogen and oxygen, coordinated to iron. Extension of this approach to other apoferritins and metals will be likely to clarify the role of cell-specific features of the apoprotein in the formation of the iron core.

Animals↗

PubMed1982

Epidemiology of penicillinase-producing Neisseria gonorrhoeae infections: analysis by auxotyping and serogrouping.

Auxotyping and serogrouping by coagglutination were used to characterize penicillinase-producing Neisseria gonorrhoeae and penicillinase-negative isolates from the state of Washington, Shreveport (Louisiana), and the Far East. Fifty-four of 75 penicillinase-producing isolates (72 per cent) from Washington required proline for growth and were serogroup W-l (Pro-1), the predominant type of penicillinase-producing strains in the Philippines; none of 86 penicillinase-negative isolates from Washington was Pro-1 (P less than 0.0001). All 38 penicillinase-producing isolates from Shreveport required proline and were serogroup W-11 (Pro-11); five of 26 penicillinase-negative isolates (19 per cent) from Shreveport were also Pro-11 (P less than 0.0001) but had antigenic specificities within serogroup W-ll that distinguished them from the penicillinase-producing isolates. We conclude that the Washington and Shreveport outbreaks resulted from the spread of imported strains rather than transmission of penicillinase-encoding plasmids to indigenous gonococci. The Shreveport outbreak involved a single strain of penicillinase-producing N, gonorrhoeae and probably originated from a common source, whereas several types were involved in the multiple-source Washington outbreak, indicating repeated introduction of new strains.

Disease Outbreaks↗

PubMed1979

Similarity of the structure of ferritin and iron . dextran (imferon) determined by extended X-ray absorption fine structure analysis.

Ferritin, a natural complex of iron oxide encased in protein, and iron . dextran, a synthetic complex of iron oxide coated with dextran, have the similar properties of maintaining high concentrations of iron in solution at physiological pH and releasing iron relatively slowly in vivo. Extended x-ray absorption fine structure (EX-AFS) analysis was performed on each complex and compared to see if the structures of the iron cores were similar. The results obtained from the extended x-ray absorption fine structure technique show that the near-neighbor environment around the average iron atom in ferritin and iron . dextran is identical, within experimental uncertainty, for the first three shells. The similarity of the iron cores in both complexes may explain the similarity of iron release in vivo. Ferritin has a protein coat which is composed of 24 subunits arranged in a hollow sphere with six channels through which the iron may move during deposition and release. However, little is known about the requirements of the protein structure in ferritin for the maintenance of high concentrations of iron in a soluble, nontoxic form or about the role of the protein in the release of iron from ferritin. The results suggest that iron . dextran will be a useful model compound in studies of the relation of the iron core and protein in ferritin to function.

Dextrans↗