Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jun 1, 1992; 89(11): 5015–5019.

Yeast flavohemoglobin is an ancient protein related to globins and a reductase family.


The hemoglobin of yeast is a two-domain protein with both heme and flavin prosthetic groups. The nucleotide sequences of the cDNA and genomic DNA encoding the protein from Saccharomyces cerevisiae show that introns are absent and that both domains are homologous with a flavoheme protein from Escherichia coli. The heme domains are also homologous with those of O2-binding heme proteins from several other distantly related bacteria, plants, and animals; all appear to be members of the same globin superfamily. Although the homologous hemoglobin of the bacterium Vitreoscilla sp. is a single-domain protein, several bacteria have related O2-binding heme proteins whose second domains have different structures and enzymatic activities: dihydropteridine reductase (E. coli), cytochrome c reductase (Alcaligenes eutrophus), and kinase in the O2 sensor of Rhizobium meliloti. This indicates that one evolutionary pathway of hemoglobin is that of a multipurpose domain attached to a variety of unrelated proteins to form molecules with different functions. The flavin domain of yeast hemoglobin is homologous with members of a flavoprotein family that includes ferredoxin reductase, nitric oxide synthase, and cytochrome P-450 reductase. The correspondence of yeast and E. coli flavohemoglobins indicates that the two-domain protein has been conserved intact for as long as 1.8 billion years, the estimated time of divergence of prokaryotes and eukaryotes provided that cross-species gene transfer has not occurred.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Wakabayashi S, Matsubara H, Webster DA. Primary sequence of a dimeric bacterial haemoglobin from Vitreoscilla. Nature. 322(6078):481–483. [PubMed]
  • Gilles-Gonzalez MA, Ditta GS, Helinski DR. A haemoprotein with kinase activity encoded by the oxygen sensor of Rhizobium meliloti. Nature. 1991 Mar 14;350(6314):170–172. [PubMed]
  • David M, Daveran ML, Batut J, Dedieu A, Domergue O, Ghai J, Hertig C, Boistard P, Kahn D. Cascade regulation of nif gene expression in Rhizobium meliloti. Cell. 1988 Aug 26;54(5):671–683. [PubMed]
  • Probst I, Wolf G, Schlegel HG. An oxygen-binding flavohemoprotein from Alcaligenes eutrophus. Biochim Biophys Acta. 1979 Feb 26;576(2):471–478. [PubMed]
  • Vasudevan SG, Armarego WL, Shaw DC, Lilley PE, Dixon NE, Poole RK. Isolation and nucleotide sequence of the hmp gene that encodes a haemoglobin-like protein in Escherichia coli K-12. Mol Gen Genet. 1991 Apr;226(1-2):49–58. [PubMed]
  • KEILIN D. Haemoglobin in fungi; occurrence of haemoglobin in yeast and the supposed stabilization of the oxygenated cytochrome oxidase. Nature. 1953 Aug 29;172(4374):390–393. [PubMed]
  • KEILIN D, TISSIERES A. Haemoglobin in moulds: Neurospora crassa and Penicillium notatum. Nature. 1953 Aug 29;172(4374):393–394. [PubMed]
  • Bogusz D, Appleby CA, Landsmann J, Dennis ES, Trinick MJ, Peacock WJ. Functioning haemoglobin genes in non-nodulating plants. Nature. 1988 Jan 14;331(6152):178–180. [PubMed]
  • Wittenberg JB, Wittenberg BA. Mechanisms of cytoplasmic hemoglobin and myoglobin function. Annu Rev Biophys Biophys Chem. 1990;19:217–241. [PubMed]
  • Vainshtein BK, Harutyunyan EH, Kuranova IP, Borisov VV, Sosfenov NI, Pavlovsky AG, Grebenko AI, Konareva NV. Structure of leghaemoglobin from lupin root nodules at 5 angstrom resolution. Nature. 1975 Mar 13;254(5496):163–164. [PubMed]
  • Dikshit KL, Spaulding D, Braun A, Webster DA. Oxygen inhibition of globin gene transcription and bacterial haemoglobin synthesis in Vitreoscilla. J Gen Microbiol. 1989 Oct;135(10):2601–2609. [PubMed]
  • Dikshit KL, Webster DA. Cloning, characterization and expression of the bacterial globin gene from Vitreoscilla in Escherichia coli. Gene. 1988 Oct 30;70(2):377–386. [PubMed]
  • Khosla C, Bailey JE. Heterologous expression of a bacterial haemoglobin improves the growth properties of recombinant Escherichia coli. Nature. 1988 Feb 18;331(6157):633–635. [PubMed]
  • Oshino R, Asakura T, Takio K, Oshino N, Chance B, Hagihara B. Purification and molecular properties of yeast hemoglobin. Eur J Biochem. 1973 Nov 15;39(2):581–590. [PubMed]
  • YCAS M. Formation of hemoglobin and the cytochromes by yeast in the presence of antimycin A. Exp Cell Res. 1956 Aug;11(1):1–6. [PubMed]
  • Waterland RA, Basu A, Chance B, Poyton RO. The isoforms of yeast cytochrome c oxidase subunit V alter the in vivo kinetic properties of the holoenzyme. J Biol Chem. 1991 Mar 5;266(7):4180–4186. [PubMed]
  • Yoshimoto A, Sakajo S, Minagawa N, Komiyama T. Possible role of a 36 kDa protein induced by respiratory inhibitors in cyanide-resistant respiration in Hansenula anomala. J Biochem. 1989 Jun;105(6):864–866. [PubMed]
  • Sakajo S, Minagawa N, Komiyama T, Yoshimoto A. Molecular cloning of cDNA for antimycin A-inducible mRNA and its role in cyanide-resistant respiration in Hansenula anomala. Biochim Biophys Acta. 1991 Aug 27;1090(1):102–108. [PubMed]
  • McEwen JE, Ko C, Kloeckner-Gruissem B, Poyton RO. Nuclear functions required for cytochrome c oxidase biogenesis in Saccharomyces cerevisiae. Characterization of mutants in 34 complementation groups. J Biol Chem. 1986 Sep 5;261(25):11872–11879. [PubMed]
  • Carlson M, Botstein D. Two differentially regulated mRNAs with different 5' ends encode secreted with intracellular forms of yeast invertase. Cell. 1982 Jan;28(1):145–154. [PubMed]
  • Arents G, Love WE. Glycera dibranchiata hemoglobin. Structure and refinement at 1.5 A resolution. J Mol Biol. 1989 Nov 5;210(1):149–161. [PubMed]
  • Bashford D, Chothia C, Lesk AM. Determinants of a protein fold. Unique features of the globin amino acid sequences. J Mol Biol. 1987 Jul 5;196(1):199–216. [PubMed]
  • Karplus PA, Daniels MJ, Herriott JR. Atomic structure of ferredoxin-NADP+ reductase: prototype for a structurally novel flavoenzyme family. Science. 1991 Jan 4;251(4989):60–66. [PubMed]
  • Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR, Snyder SH. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature. 1991 Jun 27;351(6329):714–718. [PubMed]
  • Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. [PubMed]
  • Kleinschmidt T, Sgouros JG. Hemoglobin sequences. Biol Chem Hoppe Seyler. 1987 Jun;368(6):579–615. [PubMed]
  • Konieczny A, Jensen EO, Marcker KA, Legocki AB. Molecular cloning of lupin leghemoglobin cDNA. Mol Biol Rep. 1987;12(1):61–66. [PubMed]
  • Heinemann JA, Sprague GF., Jr Bacterial conjugative plasmids mobilize DNA transfer between bacteria and yeast. Nature. 1989 Jul 20;340(6230):205–209. [PubMed]
  • Goldberg MA, Dunning SP, Bunn HF. Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. Science. 1988 Dec 9;242(4884):1412–1415. [PubMed]
  • Tyree B, Webster DA. The binding of cyanide and carbon monoxide to cytochrome o purified from Vitreoscilla. Evidence for subunit interaction in the reduced protein. J Biol Chem. 1978 Oct 10;253(19):6988–6991. [PubMed]
  • Evans T, Felsenfeld G. The erythroid-specific transcription factor Eryf1: a new finger protein. Cell. 1989 Sep 8;58(5):877–885. [PubMed]
  • Trainor CD, Evans T, Felsenfeld G, Boguski MS. Structure and evolution of a human erythroid transcription factor. Nature. 1990 Jan 4;343(6253):92–96. [PubMed]
  • Chiba T, Ikawa Y, Todokoro K. GATA-1 transactivates erythropoietin receptor gene, and erythropoietin receptor-mediated signals enhance GATA-1 gene expression. Nucleic Acids Res. 1991 Jul 25;19(14):3843–3848. [PMC free article] [PubMed]
  • Minehart PL, Magasanik B. Sequence and expression of GLN3, a positive nitrogen regulatory gene of Saccharomyces cerevisiae encoding a protein with a putative zinc finger DNA-binding domain. Mol Cell Biol. 1991 Dec;11(12):6216–6228. [PMC free article] [PubMed]
  • Cunningham TS, Cooper TG. Expression of the DAL80 gene, whose product is homologous to the GATA factors and is a negative regulator of multiple nitrogen catabolic genes in Saccharomyces cerevisiae, is sensitive to nitrogen catabolite repression. Mol Cell Biol. 1991 Dec;11(12):6205–6215. [PMC free article] [PubMed]
  • Dixon B, Walker B, Kimmins W, Pohajdak B. Isolation and sequencing of a cDNA for an unusual hemoglobin from the parasitic nematode Pseudoterranova decipiens. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5655–5659. [PMC free article] [PubMed]
  • Iwaasa H, Takagi T, Shikama K. Protozoan myoglobin from Paramecium caudatum. Its unusual amino acid sequence. J Mol Biol. 1989 Jul 20;208(2):355–358. [PubMed]
  • Iwaasa H, Takagi T, Shikama K. Protozoan hemoglobin from Tetrahymena pyriformis. Isolation, characterization, and amino acid sequence. J Biol Chem. 1990 May 25;265(15):8603–8609. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...