Aconitase, a two‐faced protein: enzyme and iron regulatory factor 1 2

  title={Aconitase, a two‐faced protein: enzyme and iron regulatory factor 1 2},
  author={Helmut Beinert and Mary Claire Kennedy},
  journal={The FASEB Journal},
  pages={1442 - 1449}
In this brief survey, the path of development of our knowledge of the iron‐sulfur enzyme aconitase [citrate(isocitrate)hydrolyase EC4.2.1.3.] is traced from its discovery in 1937, Particular emphasis is on developments in the past decade, when EPR, Mössbauer and electron nuclear double resonance spectroscopies, X‐ray crystallography, and mutational analysis were applied to the problem. More recently discovered was the significant amino acid sequence identity between mitochondrial aconitase and… 

Switching aconitase B between catalytic and regulatory modes involves iron‐dependent dimer formation

Gel filtration analysis has now shown that cell‐free extracts contain high‐molecular‐weight species of AcnB, and in vitro and in vivo protein interaction experiments have shown thatAcnB forms homodimers, suggesting a simple iron‐mediated dimerization mechanism for switching the AcNB protein between catalytic and regulatory roles.

The solution structure of apo-iron regulatory protein 1.

Adrenodoxin: Structure, stability, and electron transfer properties

The recently solved first crystal structure of the vertebrate‐type ferredoxin, the truncated adrenodoxin Adx(4‐108), is discussed, that offers the unique opportunity for better understanding of the structure‐function relationships and stabilization of this protein, as well as of the molecular architecture of [2Fe‐2S] ferredoxins in general.

Iron regulatory proteins in pathobiology.

In response to fluctuations in the level of the 'labile iron pool', IRPs act as key regulators of cellular iron homoeostasis as a result of the translational control of the expression of a number of iron metabolism-related genes.

Iron-Dependent RNA-Binding Activity of Mycobacterium tuberculosis Aconitase

The results demonstrate the bifunctional nature of M. tuberculosis Acn, pointing to its likely role in iron homeostasis.

Thioredoxin Activation of Iron Regulatory Proteins

The capacity of physiological reducing systems to cooperate with NO in the activation of IRP1 and the combined effect of NO and Trx on IRP2, which exhibits constitutive RNA binding activity are examined.

E. coli aconitase B structure reveals a HEAT-like domain with implications for protein–protein recognition

The 2.4 Å structure of E. coli AcnB reveals a high degree of conservation at the active site despite its domain reorganization, and reveals that the additional domain, characteristic of theAcnB subfamily, is a HEAT-like domain, implying a role in protein–protein recognition.

The indispensable role of mammalian iron sulfur proteins in function and regulation of multiple diverse metabolic pathways

Mechanisms of Fe–S biogenesis and delivery, and methods that will likely reveal important roles of Fe—S proteins in proteins not yet recognized as Fe-S proteins are discussed.

Iron regulatory proteins 1 and 2

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It is suggested thatIRP‐1 and IRP‐2 may bind preferenitially to certain mRNAs in vivo, possibly extending their known functions beyond the regulation of intracellular iron homeostasis.

Interaction between iron-regulatory proteins and their RNA target sequences, iron-responsive elements.

The interaction between the IRPs and the IRE represents one of the best characterised model systems for posttranscriptional gene control, and given that each IRP can also recognise its own unique set of RNAs, the search for new in vivo mRNA targets is expected to provide yet more surprises and insights into the fate of cytoplasmic mRNAs.



The soluble "high potential" type iron-sulfur protein from mitochondria is aconitase.

Engineering of protein bound iron‐sulfur clusters

An increasing number of iron-sulfur (Fe-S) proteins are found in which the Fe-S cluster is not involved in net electron transfer, as it is in the majority of Fe-S proteins. Most of the former are

Purification and characterization of cytosolic aconitase from beef liver and its relationship to the iron-responsive element binding protein.

The amino acid composition, molecular weight, isoelectric point, and the sequences of six random peptides clearly show that these physicochemical and structural characteristics are identical to those of IRE-BP, and that c-aconitase is distinctly different from m-aconitic aconitase.

19th Sir Hans Krebs lecture. Engineering of protein bound iron-sulfur clusters. A tool for the study of protein and cluster chemistry and mechanism of iron-sulfur enzymes.

Conclusions, which bear on the electronic structure of the Fe-S cluster, enzyme-substrate interaction and the enzymatic mechanism, were derived from a synopsis of the recent work described here and of previous contributions from several laboratories.

The mechanism of aconitase action. I. Preparation, physical properties of the enzyme, and activation by iron (II).

The molar relaxivity, 1/T1p[Fe], for aconitase-bound iron(III) is about half as effective as free iron (III) in relaxing the protons of water, and the inequality of the longitudinal and transverse relaxation rates indicates that protons are rapidly exchanging between bulk solvent and the coordination sphere of the iron( III).

Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: role of the iron-sulfur cluster.

The results are consistent with a model for the posttranslational regulation of the IRE-BP in which the Fe-S cluster is altered in response to the availability of intracellular iron and this, in turn, regulates the RNA-binding activity.

A mitochondrial iron protein with properties of a high-potential iron-sulfur protein.

Mutational analysis of active site residues in pig heart aconitase.

Iron-sulfur clusters in Azotobacter ferredoxin at 2.5 A resolution.

X-ray crystallographic study of the ferredoxin-like protein (iron-sulfur protein III) from Azotobacter vinelandii has been extended to 2.5-A resolution and shows two distinctly different Fe-S clusters.