Dioxygen and Hemerythrin

Stenkamp, Ronald E.

doi:10.1021/cr00027a008

Cited by 377 publications

(386 citation statements)

References 24 publications

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“…These helical motifs-or variations in which one of the His residues is converted to Glu or Asp-are frequently observed in the metal-binding sites of other monoand dinuclear Fe-, Mn-, and Zn-binding proteins. For example, the Lig-Xxx-Xxx-Xxx-Lig (in which Lig is His, Asp, or Glu) motif figures largely in the structures of hemerythrin and myohemerythrin, a class of diiron proteins involved in reversible oxygen binding and transport (63). Indeed, the backbone of myohemerythrin (64) may be described by a D 2 -symmetric model to 1.2-Å rms deviation, by using only six adjustable parameters (translations in x, y, and z, rotation of the helix about its own axis, and its tilt and inclination relative to the axis of the bundle; Table 1.…”

Section: Resultsmentioning

confidence: 99%

Retrostructural analysis of metalloproteins: Application to the design of a minimal model for diiron proteins

Lombardi

Summa

Geremia

et al. 2000

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

233

282

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De novo protein design provides an attractive approach for the construction of models to probe the features required for function of complex metalloproteins. The metal-binding sites of many metalloproteins lie between multiple elements of secondary structure, inviting a retrostructural approach to constructing minimal models of their active sites. The backbone geometries comprising the metal-binding sites of zinc fingers, diiron proteins, and rubredoxins may be described to within approximately 1 Å rms deviation by using a simple geometric model with only six adjustable parameters. These geometric models provide excellent starting points for the design of metalloproteins, as illustrated in the construction of Due Ferro 1 (DF1), a minimal model for the GluXxx-Xxx-His class of dinuclear metalloproteins. This protein was synthesized and structurally characterized as the di-Zn(II) complex by x-ray crystallography, by using data that extend to 2.5 Å. This four-helix bundle protein is comprised of two noncovalently associated helix-loop-helix motifs. The dinuclear center is formed by two bridging Glu and two chelating Glu side chains, as well as two monodentate His ligands. The primary ligands are mostly buried in the protein interior, and their geometries are stabilized by a network of hydrogen bonds to second-shell ligands. In particular, a Tyr residue forms a hydrogen bond to a chelating Glu ligand, similar to a motif found in the diiron-containing R2 subunit of Escherichia coli ribonucleotide reductase and the ferritins. DF1 also binds cobalt and iron ions and should provide an attractive model for a variety of diiron proteins that use oxygen for processes including iron storage, radical formation, and hydrocarbon oxidation. P roteins use a limited repertoire of metal ion cofactors to help catalyze a multitude of reactions. For example, diiron sites (1-4) mediate reversible oxygen binding in hemerythrins, whereas they function as hydrolytic centers in phosphatases. Structurally similar diiron sites also mediate a number of oxygendependent oxidative processes. Ferritins serve as ferroxidases, while other diiron proteins catalyze hydroxylation, epoxidation, and desaturation reactions. Further, a diiron site in Escherichia coli ribonucleotide reductase is responsible for the formation of a Tyr radical. How do the structures of these proteins tune the chemical properties of a common diiron center to obtain such a diversity of highly specific catalysts? This question is being addressed through the study of the natural proteins as well as the study of small-molecule diiron complexes (1-4). Although impressive progress has been made on both fronts, these approaches have inherent limitations. The study of large proteins is hampered by their extreme complexity, and it is difficult to synthesize small-molecule models capable of simultaneously binding diiron, oxygen, and various substrates. Recently, we and others have sought a molecular middle ground between these two extremes through the design of small proteins and peptid...

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Section: Resultsmentioning

confidence: 99%

Retrostructural analysis of metalloproteins: Application to the design of a minimal model for diiron proteins

Lombardi

Summa

Geremia

et al. 2000

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

233

282

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“…S3). In canonical Hr structures, each of the ironligating residues is positioned within an ␣-helix (14). However, in the FBXL5 Hr, helix ␣3 is relatively short and does not extend through His-80, one of the seven residues comprising the primary iron coordination shell.…”

Section: N Terminus Of Fbxl5 Adopts Hemerythrinmentioning

confidence: 99%

“…Hemerythrin (Hr) domains are characterized by an ␣-helical bundle fold that commonly contains a diiron center (14), although other metal centers are possible (Protein Data Bank (PDB) ID 2P0N) (16 -18). These iron atoms are redox-active and can switch between the fully oxidized diferric (met) state, a partially reduced semi-met state, and a fully reduced diferrous (deoxy) state.…”

mentioning

confidence: 99%

“…In canonical Hr domains, one iron atom (Fe1) is coordinated by the imidazole side chains from three histidines, whereas the other iron (Fe2) is coordinated by two histidines. Typically, a glutamate and an aspartate provide carboxylate groups that bridge Fe1 and Fe2 (14). In the deoxy state, the iron atoms are also bridged by a -hydroxo species, ostensibly derived from the solvent.…”

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confidence: 99%

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Structural and Molecular Characterization of Iron-sensing Hemerythrin-like Domain within F-box and Leucine-rich Repeat Protein 5 (FBXL5)

Thompson

Salahudeen

Chollangi

et al. 2012

Journal of Biological Chemistry

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Background: FBXL5 is required for proper regulation of cellular iron homeostasis. Results: FBXL5 contains a structurally characterized hemerythrin-like domain. Conclusion:The atypical features of the hemerythrin-like domain facilitate its role as a metabolic sensor. Significance: FBXL5 is the only identified mammalian protein containing a hemerythrin-like domain. Resolution of the structure of the domain provides mechanistic insights into its iron and oxygen responsiveness.

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“…19,20 The transformation, protonation and oxidation reactions of Fe(OEP) derivatives in DCE made in contact with W of various pH were investigated as the function of E by the group of present authors as follows, 16 and it was found that the reactions resembled largely those in biological systems.…”

Section: Methods For Measurements Of Charge Transfer Reactions At Thementioning

confidence: 99%

Biomimetic Charge Transfer Reactions at the Aqueous/Organic Solution Interface or through Artificial Membrane

et al. 2012

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Some biomimetic reactions observed with the aid of aqueous/organic, W/O, two phases or liquid membrane, LM, systems were introduced. The reactions introduced were mostly those reported by the group of present authors as follows; (1) (5) A new type of membrane transport reaction realized in the presence of an applied electrical potential gradient parallel to the W/ membrane interface. The processes of above-described reactions were elucidated based on the voltammetric methods and concepts taking into account the properties common to both artificial LMs and biomembranes. A method proposed by present authors for the elucidation of the membrane transport process was also introduced.

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Dioxygen and Hemerythrin

Cited by 377 publications

References 24 publications

Retrostructural analysis of metalloproteins: Application to the design of a minimal model for diiron proteins

Retrostructural analysis of metalloproteins: Application to the design of a minimal model for diiron proteins

Structural and Molecular Characterization of Iron-sensing Hemerythrin-like Domain within F-box and Leucine-rich Repeat Protein 5 (FBXL5)

Biomimetic Charge Transfer Reactions at the Aqueous/Organic Solution Interface or through Artificial Membrane

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