nonheme iron proteins


Summary: Proteins, usually acting in oxidation-reduction reactions, containing iron but no porphyrin groups. (Lehninger, Principles of Biochemistry, 1993, pG-10)

Top Publications

  1. Costas M, Mehn M, Jensen M, Que L. Dioxygen activation at mononuclear nonheme iron active sites: enzymes, models, and intermediates. Chem Rev. 2004;104:939-86 pubmed
  2. GALONIC D, Barr E, Walsh C, Bollinger J, Krebs C. Two interconverting Fe(IV) intermediates in aliphatic chlorination by the halogenase CytC3. Nat Chem Biol. 2007;3:113-6 pubmed
    ..The demonstration that chlorination proceeds through an Fe(IV) intermediate that cleaves a C-H bond reveals the mechanistic similarity of aliphatic halogenases to the iron- and alphaKG-dependent hydroxylases. ..
  3. Zaoui K, Benseddik K, Daou P, Salaün D, Badache A. ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells. Proc Natl Acad Sci U S A. 2010;107:18517-22 pubmed publisher
    ..By defining the signaling pathway by which ErbB2 allows MT capture and stabilization at the cell leading edge, we provide insights into the mechanism underlying cell motility and steering. ..
  4. Ozer A, Bruick R. Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one?. Nat Chem Biol. 2007;3:144-53 pubmed
    ..The discovery of protein regulation via hydroxylation raises the possibility that other Fe(II)- and 2-oxoglutarate-dependent dioxygenases might also serve in a similar capacity. ..
  5. Bruijnincx P, van Koten G, Klein Gebbink R. Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies. Chem Soc Rev. 2008;37:2716-44 pubmed publisher
    ..Sections of this review are devoted to each of these subjects, i.e. the enzymes, biomimetic models, and reactive intermediates (225 references). ..
  6. Mirica L, McCusker K, Munos J, Liu H, Klinman J. 18O kinetic isotope effects in non-heme iron enzymes: probing the nature of Fe/O2 intermediates. J Am Chem Soc. 2008;130:8122-3 pubmed publisher
    ..The comparison of the measured 18O KIEs with calculated or experimental 18O equilibrium isotope effects (18O EIEs) provides new insights into the O2 activation through an inner-sphere mechanism at a non-heme iron center. ..
  7. Friese S, Kucera B, Young V, Que L, Tolman W. Iron(II) complexes of sterically bulky alpha-ketocarboxylates. structural models for alpha-ketoacid-dependent nonheme iron halogenases. Inorg Chem. 2008;47:1324-31 pubmed publisher
    ..These results indicate that the steric hindrance useful for structural modeling of the halogenase active site prohibits functional mimicry of the enzyme. ..
  8. Straganz G, Nidetzky B. Variations of the 2-His-1-carboxylate theme in mononuclear non-heme FeII oxygenases. Chembiochem. 2006;7:1536-48 pubmed
    ..These recently discovered metallocenters are discussed with respect to their metal-binding properties and the reaction coordinates of the O(2)-dependent conversions they catalyze. ..
  9. Sorokin A, Chen J. MEMO1, a new IRS1-interacting protein, induces epithelial-mesenchymal transition in mammary epithelial cells. Oncogene. 2013;32:3130-8 pubmed publisher
    ..Together, these findings suggest that MEMO1 acts as an oncogene and is a potential therapeutic target for cancer treatment. ..

More Information


  1. Meira M, Masson R, Stagljar I, Lienhard S, Maurer F, Boulay A, et al. Memo is a cofilin-interacting protein that influences PLCgamma1 and cofilin activities, and is essential for maintaining directionality during ErbB2-induced tumor-cell migration. J Cell Sci. 2009;122:787-97 pubmed publisher
    ..In summary, these data indicate that Memo also regulates actin dynamics by interacting with cofilin and enhancing its function. ..
  2. Zaoui K, Honore S, Isnardon D, Braguer D, Badache A. Memo-RhoA-mDia1 signaling controls microtubules, the actin network, and adhesion site formation in migrating cells. J Cell Biol. 2008;183:401-8 pubmed publisher
  3. Qiu C, Lienhard S, Hynes N, Badache A, Leahy D. Memo is homologous to nonheme iron dioxygenases and binds an ErbB2-derived phosphopeptide in its vestigial active site. J Biol Chem. 2008;283:2734-40 pubmed
    ..Memo thus represents a new class of phosphotyrosine-binding protein. ..
  4. Matsumura H, Chakraborty S, Reed J, Lu Y, Moënne Loccoz P. Effect of Outer-Sphere Side Chain Substitutions on the Fate of the trans Iron-Nitrosyl Dimer in Heme/Nonheme Engineered Myoglobins (Fe(B)Mbs): Insights into the Mechanism of Denitrifying NO Reductases. Biochemistry. 2016;55:2091-9 pubmed publisher
    ..aeruginosa cNOR. ..
  5. Andreini C, Banci L, Bertini I, Elmi S, Rosato A. Non-heme iron through the three domains of life. Proteins. 2007;67:317-24 pubmed
    ..9% +/- 1.6%) and in eukaryota (1.1% +/- 0.4%). The analysis of the function of each putative iron-protein identified suggests that extant organisms have inherited the large majority of their iron-proteome from the last common ancestor. ..
  6. Nam W. High-valent iron(IV)-oxo complexes of heme and non-heme ligands in oxygenation reactions. Acc Chem Res. 2007;40:522-31 pubmed
    ..These results demonstrate how mechanistic developments in biomimetic research can help our understanding of dioxygen activation and oxygen atom transfer reactions in nature. ..
  7. Hannafon B, Sebastiani P, de las Morenas A, LU J, Rosenberg C. Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer. Breast Cancer Res. 2011;13:R24 pubmed publisher
    ..Further, we demonstrate that altered miRNA expression can modulate gene expression changes that characterize these early cancers. We conclude that miRNA dysregulation likely plays a substantial role in early breast cancer development. ..
  8. Nagashima S, Nakasako M, Dohmae N, Tsujimura M, Takio K, Odaka M, et al. Novel non-heme iron center of nitrile hydratase with a claw setting of oxygen atoms. Nat Struct Biol. 1998;5:347-51 pubmed
    ..This unprecedented structure is likely to enable the photo-regulation of NHase and will provide an excellent model for designing photo-controllable chelate complexes and, ultimately, proteins...
  9. McEvoy J, Brudvig G. Redox reactions of the non-heme iron in photosystem II: an EPR spectroscopic study. Biochemistry. 2008;47:13394-403 pubmed publisher
    ..This electron transfer might be important in the photoprotective transfer of oxidative power away from P(680)(+) and the oxygen-evolving complex in stressed PSII centers. ..
  10. Pecorelli A, Leoncini S, De Felice C, Signorini C, Cerrone C, Valacchi G, et al. Non-protein-bound iron and 4-hydroxynonenal protein adducts in classic autism. Brain Dev. 2013;35:146-54 pubmed publisher
    ..Increased levels of NPBI could contribute to lipid peroxidation and, consequently, to increased plasma and erythrocyte membranes 4-HNE PAs thus amplifying the oxidative damage, potentially contributing to the autistic phenotype. ..
  11. Au H, Scheffler I. Characterization of the gene encoding the iron-sulfur protein subunit of succinate dehydrogenase from Drosophila melanogaster. Gene. 1994;149:261-5 pubmed
    ..However, its abundance varies during development and in the major body segments of the adult fly. Pupae have very low levels of transcript, in contrast to larvae. It is most abundant in the adult thorax and low in abdominal tissues. ..
  12. Clay M, Yang T, Jenney F, Kung I, Cosper C, Krishnan R, et al. Geometries and electronic structures of cyanide adducts of the non-heme iron active site of superoxide reductases: vibrational and ENDOR studies. Biochemistry. 2006;45:427-38 pubmed
    ..The implications of these results for understanding the mechanism of SOR are discussed. ..
  13. Nanji A, Jokelainen K, Tipoe G, Rahemtulla A, Dannenberg A. Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration. J Pharmacol Exp Ther. 2001;299:638-44 pubmed
    ..The therapeutic effects of saturated fatty acids may be explained, at least in part, by reduced endotoxemia and lipid peroxidation, which in turn result in decreased activation of NF-kappaB and reduced levels of TNF-alpha and Cox-2. ..
  14. Yakunin A, Hallenbeck P. AmtB is necessary for NH(4)(+)-induced nitrogenase switch-off and ADP-ribosylation in Rhodobacter capsulatus. J Bacteriol. 2002;184:4081-8 pubmed
  15. Yin X, Zabriskie T. VioC is a non-heme iron, alpha-ketoglutarate-dependent oxygenase that catalyzes the formation of 3S-hydroxy-L-arginine during viomycin biosynthesis. Chembiochem. 2004;5:1274-7 pubmed
  16. Ravi N, Prickril B, Kurtz D, Huynh B. Spectroscopic characterization of 57Fe-reconstituted rubrerythrin, a non-heme iron protein with structural analogies to ribonucleotide reductase. Biochemistry. 1993;32:8487-91 pubmed
  17. Ishii S, Noguchi M, Miyano M, Matsumoto T, Noma M. Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase. Biochem Biophys Res Commun. 1992;182:1482-90 pubmed
    ..The other mutants retained the enzyme activity. These results strongly suggest that His-367, His-372, His-550 and Glu-376 are crucial for 5-lipoxygenase activity and coordinate to the essential iron. ..
  18. Garber Morales J, Holmes Hampton G, Miao R, Guo Y, Munck E, Lindahl P. Biophysical characterization of iron in mitochondria isolated from respiring and fermenting yeast. Biochemistry. 2010;49:5436-44 pubmed publisher
    ..The integrative approach enabled us to estimate the concentration of respiration-related proteins. ..
  19. Hallberg L, Hoppe M, Andersson M, Hulthen L. The role of meat to improve the critical iron balance during weaning. Pediatrics. 2003;111:864-70 pubmed
    ..A weaning diet with added powdered meat and AA may serve as a viable option to satisfy the body's high iron requirements during this critical period. ..
  20. Emerson J, Farquhar E, Que L. Structural "snapshots" along reaction pathways of non-heme iron enzymes. Angew Chem Int Ed Engl. 2007;46:8553-6 pubmed
  21. Shin S, Yamada K. Adequate intakes of vitamin E and protein prevent increases of oxidative damage to DNA, lipids, and protein induced by total body irradiation in mice. Nutr Cancer. 2002;44:169-174 pubmed
    ..Consumption of a VE-free diet significantly increased 8-hydroxydeoxyguanosine levels in DNA from mice fed the 1% protein diet with TBI, but such changes were not detected in DNA from mice fed the 20% protein diet. ..
  22. Deeth R, Bugg T. A density functional investigation of the extradiol cleavage mechanism in non-heme iron catechol dioxygenases. J Biol Inorg Chem. 2003;8:409-18 pubmed
    ..The subsequent collapse of the epoxide, attack by the coordinated hydroxide and final product formation proceeds with an overall exoergicity of approximately 75 kcal mol(-1) on the U4 surface. ..
  23. Chiplonkar S, Agte V. Statistical model for predicting non-heme iron bioavailability from vegetarian meals. Int J Food Sci Nutr. 2006;57:434-50 pubmed
    ..Good agreement was seen between observed and predicted dialyzability (r=0.90) and human absorption (r=0.89). The model would be useful to estimate bioavailable iron intakes of vegetarian populations and to identify at-risk individuals. ..
  24. Cotruvo J, Stubbe J. Metallation and mismetallation of iron and manganese proteins in vitro and in vivo: the class I ribonucleotide reductases as a case study. Metallomics. 2012;4:1020-36 pubmed
    ..We propose that, in many of the systems discussed, "discrimination" between metals is not performed by the protein itself, but it is instead determined by the environment in which the protein is expressed. ..
  25. Martinez C, Monso E, Quero A. [Emerging pleuropulmonary diseases associated with asbestos inhalation]. Arch Bronconeumol. 2004;40:166-77 pubmed
  26. Miyake H, Chen K, Lange S, Que L. "Intermolecular" trapping of a nonheme Fe(IV)=O intermediate. Inorg Chem. 2001;40:3534-8 pubmed
    ..These results suggest the importance of close proximity to direct the high valent metal center down a desired pathway. ..
  27. Tomchick D, Phan P, Cymborowski M, Minor W, Holman T. Structural and functional characterization of second-coordination sphere mutants of soybean lipoxygenase-1. Biochemistry. 2001;40:7509-17 pubmed
    ..The unusual and dramatic inverse solvent isotope effect (SIE) observed for the Q697E mutant indicated that an Fe(III)-OH(-) is the active site base. A new transition state model for hydrogen atom abstraction is proposed...
  28. Ryle M, Hausinger R. Non-heme iron oxygenases. Curr Opin Chem Biol. 2002;6:193-201 pubmed
    ..Spectroscopic and crystallographic studies have provided critical insights into catalysis. Self-hydroxylation reactions, commonplace in these proteins, reveal important features of metallocenter reactivity. ..
  29. Fujita Y, Tsuchiya K, Abe S, Takiguchi Y, Kubo S, Sakurai H. Estimation of the age of human bloodstains by electron paramagnetic resonance spectroscopy: long-term controlled experiment on the effects of environmental factors. Forensic Sci Int. 2005;152:39-43 pubmed
    ..Therefore, one should take such factors into account in estimating the period since bleeding by this method. ..
  30. Schmid B, Einsle O, Chiu H, Willing A, Yoshida M, Howard J, et al. Biochemical and structural characterization of the cross-linked complex of nitrogenase: comparison to the ADP-AlF4(-)-stabilized structure. Biochemistry. 2002;41:15557-65 pubmed
  31. Navas Carretero S, Perez Granados A, Sarria B, Carbajal A, Pedrosa M, Roe M, et al. Oily fish increases iron bioavailability of a phytate rich meal in young iron deficient women. J Am Coll Nutr. 2008;27:96-101 pubmed
    ..294, p = 0.011) and the fish and bean meal (R(2) = 0.401, p = 0.002). Sous vide cooked salmon fish increases iron absorption from a high phytate bean meal in humans. ..
  32. Thompson K, Molina R, Donaghey T, Brain J, Wessling Resnick M. The influence of high iron diet on rat lung manganese absorption. Toxicol Appl Pharmacol. 2006;210:17-23 pubmed
    ..In situ analysis of transferrin receptor (TfR) mRNA showed staining in BALT alone. These data demonstrate that manganese absorption from the lungs to the blood can be modified by iron status and the route of administration. ..
  33. Sinnecker S, Svensen N, Barr E, Ye S, Bollinger J, Neese F, et al. Spectroscopic and computational evaluation of the structure of the high-spin Fe(IV)-oxo intermediates in taurine: alpha-ketoglutarate dioxygenase from Escherichia coli and its His99Ala ligand variant. J Am Chem Soc. 2007;129:6168-79 pubmed
    ..This work lends credence to the idea that the combination of Mössbauer spectroscopy and DFT calculations can provide detailed structural information for reactive intermediates in the catalytic cycles of iron enzymes. ..
  34. Ning K, Zhang H, Han J, Fan H, Li J, Li R, et al. [Preparation of antibody against Memo protein and analysis of expression profile of Memo in mouse tissues]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2006;22:794-6 pubmed
    ..Antibody specific to Memo has been successfully obtained, which provides useful tool for investigation into Memo-associated mechanisms of tumor metastasis and invasiveness. ..
  35. Balibar C, Walsh C. In vitro biosynthesis of violacein from L-tryptophan by the enzymes VioA-E from Chromobacterium violaceum. Biochemistry. 2006;45:15444-57 pubmed publisher
    ..VioD hydroxylates one indole ring at the 5-position to yield proviolacein, and VioC then acts on the other indole ring at the 2-position to create the oxindole and complete violacein formation...
  36. Lawson D, Stevenson C. Structural and functional dissection of aminocoumarin antibiotic biosynthesis: a review. J Struct Funct Genomics. 2012;13:125-33 pubmed publisher
    ..The structure determinations have ranged from the routine to the challenging, necessitating a variety of different approaches. ..
  37. Kovaleva E, Neibergall M, Chakrabarty S, Lipscomb J. Finding intermediates in the O2 activation pathways of non-heme iron oxygenases. Acc Chem Res. 2007;40:475-83 pubmed
  38. Bering S, Suchdev S, Sjøltov L, Berggren A, Tetens I, Bukhave K. A lactic acid-fermented oat gruel increases non-haem iron absorption from a phytate-rich meal in healthy women of childbearing age. Br J Nutr. 2006;96:80-5 pubmed
    ..The fermented gruel increased non-haem Fe absorption from a phytate-rich meal in young women, indicating a specific effect of live L. plantarum 299v and not only an effect of the organic acids. ..
  39. Mehn M, Fujisawa K, Hegg E, Que L. Oxygen activation by nonheme iron(II) complexes: alpha-keto carboxylate versus carboxylate. J Am Chem Soc. 2003;125:7828-42 pubmed
  40. Cockrell A, McCormick S, Moore M, Chakrabarti M, Lindahl P. Mössbauer, EPR, and modeling study of iron trafficking and regulation in ?ccc1 and CCC1-up Saccharomyces cerevisiae. Biochemistry. 2014;53:2926-40 pubmed publisher
    ..The remainder is probably generated by the reduction of the vacuolar NHHS Fe(III) species. ..
  41. Hunt J, Roughead Z. Nonheme-iron absorption, fecal ferritin excretion, and blood indexes of iron status in women consuming controlled lactoovovegetarian diets for 8 wk. Am J Clin Nutr. 1999;69:944-52 pubmed
  42. Barbeito A, Garringer H, Baraibar M, Gao X, Arredondo M, Nunez M, et al. Abnormal iron metabolism and oxidative stress in mice expressing a mutant form of the ferritin light polypeptide gene. J Neurochem. 2009;109:1067-78 pubmed publisher
  43. Johnstone D, Graham R, Trinder D, Delima R, Riveros C, Olynyk J, et al. Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron loading. Brain Res. 2012;1448:144-52 pubmed publisher
  44. Shin S. Influence of the origin and level of dietary protein on TBI-induced oxidative damage in mice. Int J Vitam Nutr Res. 2003;73:297-302 pubmed
    ..Mice fed a low-protein diet became susceptible to TBI-induced oxidative damage regardless of the origin of protein. Vitamin C and E values of the soybean protein group were markedly lower than those of the casein group. ..
  45. Shin S. Vitamin E modulates radiation-induced oxidative damage in mice fed a high-lipid diet. J Biochem Mol Biol. 2003;36:190-5 pubmed
    ..Also, decreases in the GSH levels and an increase in the iron level are involved in the mechanism of this susceptibility. ..
  46. Horvathova M, Ponka P, Divoky V. Molecular basis of hereditary iron homeostasis defects. Hematology. 2010;15:96-111 pubmed publisher
    ..In addition, we will discuss molecular pathophysiology with implications for novel therapies of selected hereditary defects of iron homeostasis. ..
  47. Fukuzumi S, Kotani H, Suenobu T, Hong S, Lee Y, Nam W. Contrasting effects of axial ligands on electron-transfer versus proton-coupled electron-transfer reactions of nonheme oxoiron(IV) complexes. Chemistry. 2010;16:354-61 pubmed publisher
    ..Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 19 181-19 186). ..
  48. Chen K, Que L. Stereospecific alkane hydroxylation by non-heme iron catalysts: mechanistic evidence for an Fe(V)=O active species. J Am Chem Soc. 2001;123:6327-37 pubmed
    ..These studies thus serve as a synthetic precedent for an Fe(V)=O species in the oxygen activation mechanisms postulated for non-heme iron enzymes such as methane monooxygenase and Rieske dioxygenases. ..
  49. Sanchez Pulido L, Andrade Navarro M. The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily. BMC Biochem. 2007;8:23 pubmed
    ..This computational prediction of the function of FTO should suggest further steps for its experimental characterization and help to formulate hypothesis about the mechanisms by which it relates to obesity in humans. ..
  50. Harrington C, Elahi S, Merson S, Ponnampalavanar P. Quantitative analysis of iron-containing protein myoglobin in different foodstuffs by liquid chromatography coupled to high-resolution inductively coupled plasma mass spectrometry. J AOAC Int. 2004;87:253-8 pubmed
    ..The agreement between the 2 analytical techniques was very good. The detection limit (3 times the signal/noise ratio for a blank) of the reported method for myoglobin was 0.85 ng Fe/L. ..
  51. Kryatov S, Rybak Akimova E, Schindler S. Kinetics and mechanisms of formation and reactivity of non-heme iron oxygen intermediates. Chem Rev. 2005;105:2175-226 pubmed
  52. Decker A, Solomon E. Dioxygen activation by copper, heme and non-heme iron enzymes: comparison of electronic structures and reactivities. Curr Opin Chem Biol. 2005;9:152-63 pubmed
    ..This review compares and contrasts the electronic structures and reactivities of these various oxygen intermediates. ..
  53. Kim S, Sastri C, Seo M, Kim J, Nam W. Dioxygen activation and catalytic aerobic oxidation by a mononuclear nonheme iron(II) complex. J Am Chem Soc. 2005;127:4178-9 pubmed
    ..By carrying out 18O-labeled water experiment, we were able to conclude that the oxidation of organic substrates was mediated by an oxoiron(IV) intermediate, not by a radical type of autoxidation process. ..