Copper in Prion Octapeptide Repeats

Introduction and Perspectives
Known Mammalian Copper Enzymes: cofactors and reactions
Copper binding to repeat region of prion protein
Copper binding motifs in extracellular domains of fibroblast growth factor receptors
Occupancy of estrogen receptor 'zinc-finger' protein domain by copper
Tetra copper yeast transcription factors, AMT1, ACE1
Copper regulated promoter CUP1 in Saccharomyces cerevisiae
Lysyl oxidase and abnormalities in copper metabolism
Copper-dependent formation of miscoding etheno-DNA adducts from lipid peroxidation
Roles of the two copper ions in bovine serum amine oxidase
Monoamine oxidase gene (maoA) in Escherichia coli
Copper-zinc SOD in sporadic and familialamyotrophic lateral sclerosis
Superoxide dismutase dimer isconverted to a tetramer by val24asp in rat
A copper-effluxing ATPase, Menkes disease, and a physiological function of metallothionein
Hydrophobic patch on the plastocyanin surface
Plastocyanin: translocation and processing independent of incorporation of copper
Copper of cytochrome c oxidase at 2.8 A
Two-copper mixed-valence center of cytochrome ba3
Pseudo 2-fold symmetry in the copper-binding domain of hemocyanins
Copper centres of nitrous oxide reductase

Copper in superoxide dismutase of cow and human: amino acid sequences
Octapeptide Repeat -- typical sequences
Octapeptide Repeat DNA -- minor silent variations distinguish repeat units

Introduction and Perspectives

Prion proteins from all species investigated have a rather mysterious section early on -- an octapeptide repeated 4-5 times. Mutations with extra repeats can cause CJD. News of tight and specific copper binding to mammalian and chicken prion repeats, despite the sequence dissimilarity, opens new possibilities for understanding the structure of this region and a catalytic function for the prion protein itself. This page collects data on all known copper proteins. Homology to known copper proteins or domains may suggest a 3D structure and enzymatic function for the octapeptide repeat region.

Copper in protein generally has to do with oxidation, except for receptors, storage, transport, and regulation. Bound copper can be ligated to 4 (approximately planar) histidines or to cysteine sulfur or in other ways. I propose that the histidine scenario is applicable the prion protein repeat region, because this fits perfectly -- and explains -- the highly conserved histidine and tetra-repeat found in all prion proteins. The highly invariant adjacent proline provides rigidity, and the nonapeptide is perhaps a spacer on a pseudo-pentamer. If verified, this suggests an oxidative capability for prion protein (that can get out of hand if conformally deregulated, damaging neurons in BSE and CJD).

The abundant glycine in the octapeptide mammalian repeat avoids steric hinderance but may not be especially significant. For example, chickens are PHNPGY x 9 and closer to home, a marsupial is PHPGGSSWGQ. For mammalian genetics, the issue is the DNA's high GC content and apparently consequent slipping and back-hybridizing of newly synthesized DNA during replication, which results in a wide varity of CJD-causing repeat insertions and deletions. -- webmaster


Known Copper Enzymes

Adapted from the Swiss molecular biology server EXPASY at Geneva.

Each protein cofactors has its own page.
Links on the EC classification give reactants, comments, and cross references.

EC ClassEnzyme NameOther Cofactors
1.1.3.5 HEXOSE OXIDASE
1.1.3.9 GALACTOSE OXIDASE
1.3.99.8 2-FUROYL-COA DEHYDROGENASE
1.4.3.6 AMINE OXIDASE6-HYDROXYDOPA
1.4.3.14 L-LYSINE OXIDASEPQQ
1.7.2.1 NITRITE REDUCTASE (CYTOCHROME)
1.7.3.3 URATE OXIDASE
1.7.99.3 NITRITE REDUCTASEFAD
1.7.99.6 NITROUS-OXIDE REDUCTASE
1.9.3.1 CYTOCHROME-C OXIDASE
1.10.3.1 CATECHOL OXIDASE
1.10.3.2 LACCASE
1.10.3.3 L-ASCORBATE OXIDASE
1.13.11.17 INDOLE 2,3-DIOXYGENASEFLAVOPROTEIN
1.13.11.24 QUERCETIN 2,3-DIOXYGENASE
1.14.17.1 DOPAMINE-BETA-MONOOXYGENASE
1.14.17.3 PEPTIDYLGLYCINE MONOOXYGENASE
1.14.18.1 MONOPHENOL MONOOXYGENASE
1.15.1.1 SUPEROXIDE DISMUTASEZn, Fe, or Mn
1.16.3.1 FERROXIDASE

Copper binding to the N-terminal tandem repeat regions of mammalian and avian prion protein
Hornshaw MP; McDermott JR; Candy JM
Biochem Biophys Res Commun 207: 621-9 (1995)

We have shown, using mass spectrometry, that synthetic peptides containing three or four copies of an octapeptide repeat sequence (PHGGGWGQ), found in a highly conserved N-terminal domain of PrP, preferentially bind copper over other metals. Peptides from the analogous region of chicken PrP, which contains an N-terminal repeat domain of the hexapeptide (NPGYPH), showed similar specificity for copper binding. In addition, gel filtration chromatography demonstrated concentration dependent binding of copper to the mammalian tetra repeat PrP peptide. These results suggest that PrP may be a copper binding protein in vivo.


Copper binding to repeat region of mammalian and avian prion protein: structural studies

Hornshaw MP; McDermott JR; Candy JM; Lakey JH
Biochem Biophys Res Commun 214: 993-9 (1995)

Using CD spectroscopy we have investigated the effect of Cu2+ on the secondary structure of synthetic peptides Octa4 and Hexa4 corresponding to tetra-repeats of the octapeptide of mammalian PrP and the hexapeptide of chicken PrP. In addition, fluorescence spectroscopy was used to estimate the dissociation constants (Kd), of Cu2+ binding by both peptides. Both peptides exhibited unusual CD spectra, complicated by the high proportion of aromatic residues, revealing little secondary structure in aqueous solution. Addition of Cu2+ to Hexa4 induced an increase in random coil to resemble Octa4. The fluorescence of both peptides was quenched by Cu2+ and this was used to calculate Kd's of 6.7 microM for Octa4 and 4.5 microM for Hexa4. Other divalent cations showed lesser effects on the fluorescence of the peptides.

Copper and calcium binding motifs in the extracellular domains of fibroblast growth factor receptors

Patstone G; Maher P Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA. J Biol Chem 271: 3343-6 (1996) High affinity fibroblast growth factor (FGF) receptors contain a cluster of acidic amino acids in their extracellular domains that is reminiscent of the calcium binding domains of some cell adhesion molecules. Based on this observation, we used a calcium blotting technique to show that FGFR-1 binds calcium and that calcium binding is not observed in a mutagenized form of the receptor that lacks the acidic box region. The acidic box also binds other divalent cations, including copper. This latter interaction appears unique since the binding of copper to FGFR-1 mediates the binding of the receptor to immobilized heparin. While this observation may help explain the angiogenic properties of copper, divalent cation binding to FGF receptors may also mediate the interaction between FGF receptors, cell adhesion molecules and other proteoglycan components of the extracellular matrix.

Azurin copper sites in a His46Gly mutant

van Pouderoyen G; Andrew CR; Loehr TM; Sanders-Loehr J; Mazumdar S; Hill HA; Canters GW Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, The Netherlands. Biochemistry 35: 1397-407 (1996)
The spectroscopic and mechanistic properties of the Cu-containing active site of azurin from Pseudomonas aeruginosa were investigated by the construction of a mutant in which one of the ligands of the metal, His46, was replaced by a glycine. Although the mutation creates a hole in the interior of the protein, the 3D structure of the protein does not change to any appreciable extent. However, the spectroscopic (optical, resonance Raman, EPR) properties of the mutant protein are strongly affected by the mutation. In the presence of external ligands, the properties of the original wild-type protein are restored to a smaller or larger extent, depending on the ligand. It is concluded that the hole created by the mutation, even though it is completely buried inside the protein, can be filled by external ligands, often resulting in the creation of a mixture of so-called type-1 and type-2 copper sites. Also, the redox properties (midpoint potential, kinetics of reduction/oxidation) appeared to be strongly affected by the mutation and the presence of external ligands.

The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 A

Tsukihara T; Aoyama H; Yamashita E; Tomizaki T; Yamaguchi H; Shinzawa-Itoh K; Nakashima R; Yaono R; Yoshikawa S Institute for Protein Research, Osaka University, Suita, Japan. Science 272: 1136-44 (1996)
The crystal structure of bovine heart cytochrome c oxidase at 2.8 A resolution with an R value of 19.9 percent reveals 13 subunits, each different from the other, five phosphatidyl ethanolamines, three phosphatidyl glycerols and two cholates, two hemes A, and three copper, one magnesium, and one zinc. Of 3606 amino acid residues in the dimer, 3560 have been converged to a reasonable structure by refinement. A hydrogen-bonded system, including a propionate of a heme A (heme a), part of peptide backbone, and an imidazole ligand of CuA, could provide an electron transfer pathway between Cu A and heme a.

Monoamine oxidase gene (maoA) in Escherichia coli

Yamashita M; Azakami H; Yokoro N; Roh JH; Suzuki H; Kumagai H; Murooka Y Department of Biotechnology, Graduate School of Engineering, Osaka University, Japan. J Bacteriol 178: 2941-7 (1996)
The structural gene for copper- and topa quinone-containing monoamine oxidase (maoA) and an unknown amine oxidase gene have been located at 30.9 min on the Escherichia coli chromosome. A single open reading frame (maoB) consisting of 903 bp was found. The gene encoded a polypeptide with a predicted molecular mass of 34,619. No homology of the nucleotide sequence of maoB to the sequences of any reported genes was found. However, the amino acid sequence of MaoB showed a high level of homology with respect to the helix-turn-helix motif of the AraC family in its C terminus. The homology search and disruption of maoA on the chromosome led to the conclusion that MaoB is a transcriptional activator of maoA but not an amine oxidase. The maoA gene is regulated by tyramine and MaoB and the expression of the maoB gene is subject to catabolite repression.

Distinguishing sporadic from familial amyotrophic lateral sclerosis

Orrell RW; Habgood J; Rudge P; Lane RJ; de Belleroche JS Department of Biochemistry, Charing Cross and Westminister Medical School, London, England. Ann Neurol 39: 810-2 (1996)
Mutations of the copper/zinc superoxide dismutase (SOD-1) gene are present in around 20% of patients with a family history of amyotrophic lateral sclerosis. The finding of these mutations in patients with sporadic amyotrophic lateral sclerosis is rare. We describe a family with amyotrophic lateral sclerosis associated with the SOD-1 mutation Asp 101 Asn. This mutation was previously described as occurring in a patient with sporadic disease. We discuss the difficulties in defining truly sporadic amyotrophic lateral sclerosis, and the consequent implications on the neurogenetic advice given to other family members.

Amyotrophic lateral sclerosis: homozygous NAIP deletion in a sporadic case

Jackson M; Morrison KE; Al-Chalabi A; Bakker M; Leigh PN Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK. Ann Neurol 39: 796-800 (1996)
Although defects in the gene encoding the enzyme cytosolic copper/zinc superoxide dismutase (SOD1) have been reported in 20% of familial amyotrophic lateral sclerosis (ALS) patients, the etiology of the remaining familial cases and the more common sporadic form of the disease remains unknown. Recently, deletions of the neuronal apoptosis inhibitory protein gene NAIP, of the survival motor neuron gene SMN, and of a further cDNA fragment, XS2G3, have been reported in childhood-onset proximal spinal muscular atrophy (SMA), another disorder with pathology restricted to the motor system. We have therefore investigated the possibility of alterations in SMN and NAIP in 154 patients with ALS (135 sporadic cases, 17 familial cases). None of these patients revealed mutations in SMN.

Rat extracellular superoxide dismutase dimer is converted to a tetramer by val24asp.

Carlsson LM; Marklund SL; Edlund T Department of Clinical Chemistry, Umea University Hospital, Sweden. Proc Natl Acad Sci U S A 93: 5219-22 (1996)
Extracellular superoxide dismutase (EC-SOD) is a secreted Cu and Zn-containing glycoprotein. While EC-SOD from most mammals is tetrameric, rat EC-SOD is apparently dimeric. Analysis of a series of chimeric and point mutated EC-SODs showed that the N-terminal region contributes to the oligomeric state of the EC-SODs, and that a single amino acid, a valine (human amino acid position 24), is essential for the tetramerization. This residue is replaced by an aspartate in the rat. Rat EC-SOD carrying an Asp --> Val mutation is tetrameric. Thus, the rat EC-SOD dimer is converted to a tetramer by the exchange of a single amino acid. These results also suggest that tetrameric EC-SODs are not symmetrical tetrahedrons, but composed of two interacting dimers, further supporting an evolutionary relationship with the dimeric cytosolic Cu and Zn-containing SODs.

Lysyl oxidase, procollagen, and Menkes and occipital horn syndromes

Kemppainen R; Hamalainen ER; Kuivaniemi H; Tromp G; Pihlajaniemi T; Kivirikko KI Collagen Research Unit, Department of Medical Biochemistry, University of Oulu, Finland. Arch Biochem Biophys 328: 101-6 (1996)
The Menkes syndrome and the occipital horn syndrome are two X-linked recessively inherited disorders characterized by . These abnormalities are associated with a reduction in the activity of lysyl oxidase, an extracellular copper enzyme that initiates the cross-linking.

A copper-effluxing ATPase, Menkes disease, and a physiological function of metallothionein

Kelly EJ; Palmiter RD Department of Biochemistry, University of Washington, Seattle 98195-7370, USA. Nat Genet 13: 219-22 (1996)
Human Menkes disease and the murine Mottled phenotype are X-linked diseases that result from copper deficiency due to mutations in , designated ATP7A. Male mice with the Mottled-Brindled allele (Mo-brJ) accumulate copper in the intestine, fail to export copper to peripheral organs and die a few weeks after birth. Mu

Plastocyanin, cytochrome c and the hydrophobic patch on the plastocyanin surface

Qin L; Kostic NM Department of Chemistry, Iowa State University, Ames 50011, USA. Biochemistry 35: 3379-86 (1996)
The acidic patch in cupriplastocyanin is directly cross-linked to the basic patch in ferricytochrome c. The triplet state of zinc cytochrome c reduces the pc(II) moiety, not the cyt(III) moiety, of the covalent complex. At high ionic strength, at which electrostatic interactions are practically abolished, the blue copper site is reduced with approximately equal rates via the hydrophobic patch in the pc(II) moiety of the complex and via the acidic patch in free pc(II).

Transit peptide sequence of plastocyanin in expression, processing, and copper-binding activity

Hibino T; Lee BH; Takabe T Department of Chemistry, Faculty of Science & Technology, Meijo University, Aichi. J Biochem (Tokyo) 116: 826-32 (1994)
Plastocyanin is a copper protein that functions as an electron carrier in the thylakoid lumen of the chloroplast. To characterize the transit peptide of plastocyanin and develop expression systems for it in Escherichia coli. When the full-length cDNA encoding the precursor plastocyanin from Silene pratensis was expressed in E. coli, a large amount of precursor plastocyanin accumulated in insoluble aggregates. Its accumulation level was increased by the addition of copper ions. About six percent of precursor plastocyanin molecules were transported into the periplasmic space and processed to the mature protein. On the other hand, expression of the intermediate size cDNA, which contains the hydrophobic domain and basic amino acid of C-terminal transit peptide, caused exclusive translocation to the periplasmic space and correct processing to the mature size. The addition of copper ions increased the holo-protein content, but did not change the polypeptide content of mature plastocyanin, indicating that translocation and processing are independent of the incorporation of copper ions.

Copper-dependent formation of miscoding etheno-DNA adducts

Nair J; Sone H; Nagao M; Barbin A; Bartsch H German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, Germany. Cancer Res 56: 1267-71 (1996)
hereditary abnormal copper metabolism, which develop spontaneous hepatitis and later hepatocellular carcinoma. Etheno adduct levels in LEC rats were well correlated with the hepatic copper levels, and peak adduct levels coincided with the age of commencement of fulminant hepatitis. Our results demonstrate for the first time a copper- and age-dependent formation of highly miscoding etheno-DNA adducts in the liver of LEC rats. These adducts are formed from lipid peroxidation products (F. El-Ghissassi et al., Chem. Res. Toxicol., 8: 273-283, 1995) and thus could arise in the liver of LEC rats from oxygen radicals generated by copper-catalyzed Fenton-type reactions. Etheno-DNA adducts along with other oxidative DNA base damages may thus be involved in liver carcinogenesis in LEC rats.

Cu A-domain of the cytochrome ba3 from Thermus thermophilus

Slutter CE; Sanders D; Wittung P; Malmstrom BG; Aasa R; Richards JH; Gray HB; Fee JA Division of Chemistry and Chemical Engineering, California Institute ofTechnology, Pasadena, 91125, USA. Biochemistry 35: 3387-95 (1996)
Recently, the genes of cytochrome ba3 from Thermus thermophilus, a homolog of the heme-copper oxidase family, have been cloned. We report here expression of a truncated gene, encoding the copper A (CuA) domain of cytochrome ba3, that is regulated by a T7 RNA polymerase promoter in Escherichia coli. The CuA-containing domain is purified in high yields as a water-soluble, thermostable, purple-colored protein. Copper analysis by chemical assay, mass spectrometry, X-ray fluorescence, and EPR spin quantification show that this protein contains two copper ions bound in a mixed-valence state, indicating that the Cu A site in cytochrome ba3, is a binuclear center.

A Zn(II) site in the copper-responsive yeast transcription factor, AMT1: a conserved Zn module

Farrell RA; Thorvaldsen JL; Winge DR University of Utah Health Sciences Center, Salt Lake City 84132, USA. Biochemistry 35: 1571-80 (1996)
The N-terminal metal-binding domains of the copper-activated yeast transcription factors, ACE1 and AMT1, bind to specific DNA sequences in a Cu-dependent fashion. Recombinant AMT1 and ACE1 metal-binding domains are isolated as Cu4 Zn1-protein complexes. Site-directed mutagenesis of AMT1 was used in this study to map the ligands of the Cu(I) and Zn(II) ions. The results are consistent with the N-terminal halves of AMT1 and ACE1 consisting of two independent submodules, one binding a single Zn(II) ion and the second binding the tetracopper cluster. The basis of this conclusion is, first, that mutations of two cysteinyl codons and a histidyl codon in the first 42 residues of AMT1 do not alter DNA binding. In contrast, serine substitutions at four cysteine positions at codons 43, 61, 90, and 98 abolish DNA binding. We demonstrated previously that population of the Zn(II) site in AMT1 does not alter the ability of the protein to bind DNA but bound Cu(I) ions are essential for DNA binding [Thorvaldsen, J. L., et al. (1994) Biochemistry 33, 9566-9577]. Second, mutations in the N-terminal 42 residue segment reduce the Zn(II) content of purified mutant AMT1 molecules. The divalent metal site consists of ligands provided by three cysteinyl thiolates and a single histydyl imidazole. Thus, AMT1 and likely ACE1 consist of two contiguous modules, residues 1-42 forming an independent Zn(II) module and residues 43-110 enfolding a tetracopper cluster.

Occupancy of a C2-C2 type 'zinc-finger' protein domain by copper

Hutchens TW; Allen MH; Li CM; Yip TT Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030. FEBS Lett 309: 170-4 (1992)
The metal ion specificity of most 'zinc-finger' metal binding domains is unknown. The human estrogen receptor protein contains two different C2-C2 type 'zinc-finger' sequences within its DNA-binding domain (ERDBD). Copper inhibits the function of this protein by mechanisms which remain unclear. We have used electrospray ionization mass spectrometry to evaluate directly the 71-residue ERDBD which showed a high affinity for Cu and was completely occupied with 4 Cu bound; each Cu ion was evidently bound to only two ligand residues (net loss of only 2 Da per bound Cu). The Cu binding stoichiometry was confirmed by atomic absorption. These results (i) provide the first direct physical evidence for the ability of the estrogen receptor DNA-binding domain to bind Cu and (ii) document a twofold difference in the Zn- and Cu-binding capacity. Differences in the ERDBD domain structure with bound Zn and Cu are predicted. s

Roles of the two copper ions in bovine serum amine oxidase

Suzuki S; Sakurai T; Nakahara A Biochemistry 25: 339-41 (1986)
With a view to obtaining information on the roles of the two copper ions in bovine serum amine oxidase (BSAO), spectroscopic and magnetic studies on several BSAO derivatives have been carried out, reveaingl that two copper ions in the enzyme molecule are environmentally identical.

Pseudo 2-fold symmetry in the copper-binding domain of arthropodan haemocyanins

Volbeda A; Hol WG Department of Chemistry, University of Groningen, The Netherlands. J Mol Biol 206: 531-46 (1989)
Investigation of the copper-binding centre of Panulirus interruptus haemocyanin led to the discovery of a pseudo 2-fold axis relating two helical pairs surrounding and co-ordinating the two copper ions. The pseudo 2-fold symmetry relating one helical pair, co-ordinating Cu-A, to the second helical pair co-ordinating Cu-B is quite precise with 31 equivalent C alpha atoms having a root-mean-square deviation of only 1.47 A. The 2-fold consists of a rotation of 174.6 degrees and a translation parallel to the rotation axis of 0.7 A. After superposition of the helical pairs, the two copper ions are within 1.1 A and the three C alpha atoms of the histidine ligands of Cu-A are within a root-mean-square deviation of 1.0 A from the C alpha atoms of the histidine residues co-ordinating Cu-B. Of the superimposed residues, 26% are identical in sequence. These data suggest that the current oxygen-binding centre of arthropodan haemocyanins is the result of dimerization, gene duplication and gene fusion of an ancestral mono-copper-binding helical pair.In the sequence of functional domains of molluscan haemocyanins only amino acid sequence homology with the arthropodan Cu-B helical pair has been found and no evidence for similarity with a Cu-A binding helical pair was observed. This provides strong evidence that a mono-copper-binding helical pair has been the ancestor of both the arthropodan and molluscan haemocyanins. Haemerythrins are less similar to each other than the two Cu-binding helical pairs in arthropodan haemocyanins. Nevertheless, the Fe-B haemerythrin helical pair superimposes well onto the Cu-A helical pair of Panulirus haemocyanin. A root-mean-square deviation of 1.9 A for 24 equivalent C alpha carbon atoms is obtained, while Fe-B deviates 1.4 A from Cu-A after superposition of the helices. Moreover, the three histidine ligands of the Cu-A helical pair are equivalent with three histidine ligands of the Fe-B pair. The structural similarity and correspondence in metal-binding ligands suggests that both haemocyanins and haemerythrins have originated from an ancestral mono-metal-binding helical pair having two ligands provided by the first helix and one ligand by the second helix.

Copper centres of nitrous oxide reductase

Farrar JA; Thomson AJ; Cheesman MR; Dooley DM; Zumft WG Centre for Metalloprotein Spectroscopy and Biology, School of Chemical Sciences, University of East Anglia, Norwich, UK. FEBS Lett 294: 11-5 (1991)
Nitrous oxide reductase, Pseudomonas stutzeri, catalyses the 2 electron reduction of nitrous oxide to di-nitrogen. The enzyme has 2 identical subunits (Mr approximately 70,000) of known amino acid sequence and contains approximately 4 Cu ions per subunit. The enzyme contains 2 distinct copper centres of which one is assigned to an electron-transfer function, centre A, and the other to a catalytic site, centre Z. The latter is a binuclear copper centre with at least 1 cysteine ligand and cycles between oxidation levels Cu(II)/Cu(II) and Cu(II)/Cu(I) in the absence of substrate or inhibitors.

Ubiquitin fusion products under the control of the copper regulated promoter CUP1 in Saccharomyces cerevisiae.


Prion Protein Octapeptide Repeats

Octapeptide Repeat -- typical amino acid sequences
chickenHRQPSY PRQPGY PHNPGY PHNPGY PHNPGY PHNPGY PHNPGY PQNPGY PHNPGY
marsupialPQGGGTNWGQ PHPGGSNWGQ PHPGGSSWGQ PHGGSNWGQ
mammalPQGGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGGWGQ
mammalPQGGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGGWGQ
mammalPQGGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ
mammalPQGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ
mammalPSQGGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGWGQ PHGGGGWGQ


Octapeptide Repeat DNA -- minor silent variations distinguish repeat units
cct cag gga ggg gtg gct ggg gtc cag R1 bovine
ccc cat gga ggt ggc tgg ggc cag R2
cct cat gga ggt ggc tgg ggc cag R3*
cct cat gga ggt ggc tgg ggt cag R4
ccc cat ggt ggt ggc tgg gga cag R3
cca cat ggt ggt gga ggc tgg ggt caa R6

cct cag ggc ggt ggt ggc tgg ggg cag human
cct cat ggt ggt ggc tgg ggg cag
cct cat ggt ggt ggc tgg ggg cag
ccc cat ggt ggt ggc tgg gga cag
cct cat ggt ggt ggc tgg ggt caa

cct cag ggc ggt ggt ggc tgg ggg cag R1 human del
cct cat ggt ggt ggc tgg ggg cag R2
cct cat ggt ggt ggc tgg ggg cag R2
ccc cat ggt ggt ggc tgg ggt caa R3-4


Copper-containing superoxide dismutase of cow and human: aa sequences

human sod

MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLH GFHVHEFGDNTAGCTSAGPHFNPLSRKHHVGDLGNVTADKDGVADVSIEG SVISLSGDHCIIGRTLVV H EKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ

cow sod

MLSRAACSTSRRLVPALSVLGSRQK H SLPDLPYDYGALEP H INA QIMQLHH SKHHAAYVNNLNVAEEKYREALEKGDVTAQIALQPALKFNGGG H IN H SIFW TNLSPNGGGEPQGELLEAIKRDFGSPAKFKEKLTAVSVGVQGSGWGWLGFNKEQGRLQ IAACSNQDPLQGTTGLIPLLGIDVWEHAYYLQYKNVRPDYLKAIWNVINWENVTARYT ACSK

e coli sod

MKRFSLAILALVVATGAQAASEKVEMNLVTSQGVGQSIGSVTIT ETDKGLEFSPDLKALPPGEHGFHIH AKGSCQPATKDGKASAAESAGGHHEGPEGAGHLGDLPALVVNNDGKATDAVIAPRLKSLDEIKDKALMVHVGGDNMSDQPKPL GGGGERYACGVIK