The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Chemical Compound Review

AC1NUTSJ     2-aminoethanoic acid

Synonyms: Gly(.), CHEBI:32721, glycine radical, amino(carboxy)methyl
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of glycine radical

  • The glycyl radical enzymes include pyruvate formate-lyase, anaerobic ribonucleotide reductase from Escherichia coli, and benzylsuccinate synthase [1].
  • We show here that the mutation Gly 90-->Asp (G90D) in the second transmembrane segment of rhodopsin, which causes congenital night blindness, also constitutively activates opsin [2].
  • We have analyzed how the immune system generates antibodies that are specific for analogues of an epitope on the influenza virus hemagglutinin (HA) that differ solely by the presence of Asp or Gly at amino acid 225 [3].
  • We investigated whether an alpha-adducin polymorphism (Gly 460 Trp) is involved in essential hypertension in two separate populations [4].
  • These cleavage sites or gene product boundaries are defined by the heptapeptide sequence...Glu-Xaa-Xaa-Tyr-Xaa-Gln-Ser or Gly.... We have used the 54 kd Mr nuclear inclusion protein/30 kd Mr capsid protein junction as a model to examine the role of these conserved amino acids in defining a cleavage site [5].
 

Psychiatry related information on glycine radical

 

High impact information on glycine radical

  • 3. Sequencing of the loricrin gene revealed an insertion that shifts the translation frame of the C-terminal Gly- and Gln/Lys-rich domains, and is likely to impair cornification [7].
  • We report the association of a single heterozygous Gly to Ser missense mutation in the glucagon receptor gene with late-onset NIDDM [8].
  • Mutation of Tyr-751 to Phe or Gly, or mutation of the catalytic domain to abolish kinase activity, blocked association of the PDGF-R with the PI kinase and the three proteins [9].
  • Catecholamines stimulate cardiac contractility through beta(1)-adrenergic receptors (beta(1)-ARs), which in humans are polymorphic at amino acid residue 389 (Arg/Gly) [10].
  • We have previously demonstrated that the pentapeptide Asp/Glu-Trp-Asp/Glu-Tyr-Ser/Gly is a molecular mimic of double-stranded DNA [11].
 

Chemical compound and disease context of glycine radical

 

Biological context of glycine radical

  • Oncogenic ras-encoded proteins differ from their normal homologues by an amino acid substitution for Gly 12, Ala 59 or Gln 61 [17].
  • Most mutations causing an amino-acid substitution for Gly 12 result in decreased GTPase activity and produce a transforming phenotype [18].
  • Substitution of Gly 145 in BH1 domain or Trp 188 in BH2 domain completely abrogated Bcl-2's death-repressor activity in interleukin-3 deprivation, gamma-irradiation and glucocorticoid-induced apoptosis [19].
  • The structure of a class III enzyme suggests a common origin for the three classes but shows differences in the active site that can be understood on the basis of the radical-initiation system and source of reductive electrons, as well as a unique protein glycyl radical site [20].
  • A point mutation in the alpha-chain gene was identified that results in the substitution of Gly with Ser in eight Ashkenazi adult GM2 gangliosidosis patients from five different families [21].
 

Anatomical context of glycine radical

  • The molecular basis for the little (lit) mouse phenotype, characterized by a hypoplastic anterior pituitary gland, is the mutation of a single nucleotide that alters Asp 60 to Gly in the growth hormone releasing factor receptor [22].
  • This observation is consistent with the interpretation that Gly spaces the B beta 7-14 away from self to form an antigenic determinant complementary to strain 13 T cell antigen recognition structures [23].
  • However, EBNA1 is invisible to CD8(+) cytotoxic T lymphocytes because its Gly/Ala repeat domain prevents proteasome-dependent processing for presentation on major histocompatibility complex (MHC) class I. We now describe that CD4(+) T cells from healthy adults are primed to EBNA1 [24].
  • In higher plants, photorespiratory Gly oxidation in leaf mitochondria yields ammonium in large amounts [25].
  • In five HypoPP families without DHPR gene defects, we identified two mutations, Arg-672-->His and -->Gly, in the voltage sensor of domain 2 of a different protein: the skeletal muscle sodium channel alpha subunit, known to be responsible for hereditary muscle diseases associated with myotonia [26].
 

Associations of glycine radical with other chemical compounds

  • First, the carboxy-terminal Arg residue of newly synthesized Apg8 is removed by Apg4/Aut2, a novel cysteine protease, and a Gly residue becomes the carboxy-terminal residue of the protein that is now designated Apg8FG [27].
  • Purified intact mitochondria efficiently use Gly oxidation (as sole energy, NH(3), and CO(2) source) to drive conversion of l-Orn to l-citrulline, an ATP-dependent process [25].
  • To identify the apo-B100 Cys residue involved in the formation of Lp(a), we constructed a yeast artificial chromosome (YAC) spanning the human apo-B gene and used gene-targeting techniques to change Cys-4326 to Gly [28].
  • This enzyme, which has an apparent molecular mass of 100 kDa, performs a selective cleavage at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bond (Xaa = Ser, Phe, Tyr, His, or Gly) of a number of peptide hormones, including atrial natriuretic factor, substance P, angiotensin II, bradykinin, somatostatin, neuromedins B and C, and litorin [29].
  • This nucleotide change causes a single amino acid substitution from Gly to Val at the 157th position, which is located in the NH2-terminal domain of the enzyme [30].
 

Gene context of glycine radical

  • Achondroplasia has recently been shown to result from a Gly to Arg substitution in the transmembrane domain of the fibroblast growth factor receptor 3 (FGFR3), although the molecular consequences of this mutation have not been investigated [31].
  • Ufm1 is first cleaved at the C-terminus to expose its conserved Gly residue [32].
  • The SIP1 sip2Delta gal83Delta strain manifests a subset of Snf phenotypes (Raf(+), Gly(-)) observed in the snf1Delta 10 strain (Raf(-), Gly(-)), suggesting that individual beta-subunits direct the Snf1 kinase to a subset of its targets in vivo [33].
  • An early onset colorectal tumor is heterozygous for the analogous Gly --> Ser mutation in hMSH2, and a second hMSH2 mutation was not found, suggesting that this missense mutation may predispose to cancer via a dominant mutator effect [34].
  • The mutator effects of the deletion mutant and the Gly --> Ala missense mutant in yeast MSH2 are enhanced by heterozygosity for a missense mutation in DNA polymerase delta that reduces its proofreading activity but is not a mutator in the heterozygous state [34].
 

Analytical, diagnostic and therapeutic context of glycine radical

  • Circular dichroism spectroscopy indicates that the extent of helicity of these peptides follows the order Ala greater than Leu greater than Met greater than Gln greater than Ile greater than Val greater than Ser greater than Thr greater than Asn greater than Gly [35].
  • Within this peptide segment, Tyr284, Tyr287, Tyr309, Trp310 and Trp312 were separately substituted into Gly and Tyr287 into Phe by site-directed mutagenesis [36].
  • Pro was mutagenized to Glu and to Gly using a two-step recombinant polymerase chain reaction procedure, and the mutant proteins were expressed in vitro [37].
  • Asp-101 and Trp-62 of HEL, whose conformations are perturbed by the binding of antibody HyHEL10 in this interaction, were replaced with Gly, and the resulting interactions were studied by assay of the inhibition of the lysozyme activity with the Fv fragment and by titration calorimetry [38].
  • Activated NrdD was separated from NrdG by anaerobic affinity chromatography on dATP-Sepharose without loss of its glycyl radical [39].

References

  1. Radical mechanisms of enzymatic catalysis. Frey, P.A. Annu. Rev. Biochem. (2001) [Pubmed]
  2. Rhodopsin mutation G90D and a molecular mechanism for congenital night blindness. Rao, V.R., Cohen, G.B., Oprian, D.D. Nature (1994) [Pubmed]
  3. Antibodies that are specific for a single amino acid interchange in a protein epitope use structurally distinct variable regions. Stark, S.E., Caton, A.J. J. Exp. Med. (1991) [Pubmed]
  4. Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Cusi, D., Barlassina, C., Azzani, T., Casari, G., Citterio, L., Devoto, M., Glorioso, N., Lanzani, C., Manunta, P., Righetti, M., Rivera, R., Stella, P., Troffa, C., Zagato, L., Bianchi, G. Lancet (1997) [Pubmed]
  5. Biochemical and mutational analysis of a plant virus polyprotein cleavage site. Dougherty, W.G., Carrington, J.C., Cary, S.M., Parks, T.D. EMBO J. (1988) [Pubmed]
  6. Clinical aspects of amyloidosis, including related proteins and central nervous system amyloid. Cohen, A.S. Current opinion in rheumatology. (1994) [Pubmed]
  7. A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome. Maestrini, E., Monaco, A.P., McGrath, J.A., Ishida-Yamamoto, A., Camisa, C., Hovnanian, A., Weeks, D.E., Lathrop, M., Uitto, J., Christiano, A.M. Nat. Genet. (1996) [Pubmed]
  8. A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus. Hager, J., Hansen, L., Vaisse, C., Vionnet, N., Philippi, A., Poller, W., Velho, G., Carcassi, C., Contu, L., Julier, C. Nat. Genet. (1995) [Pubmed]
  9. Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins. Kazlauskas, A., Cooper, J.A. Cell (1989) [Pubmed]
  10. Beta 1-adrenergic receptor polymorphisms confer differential function and predisposition to heart failure. Mialet Perez, J., Rathz, D.A., Petrashevskaya, N.N., Hahn, H.S., Wagoner, L.E., Schwartz, A., Dorn, G.W., Liggett, S.B. Nat. Med. (2003) [Pubmed]
  11. A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. DeGiorgio, L.A., Konstantinov, K.N., Lee, S.C., Hardin, J.A., Volpe, B.T., Diamond, B. Nat. Med. (2001) [Pubmed]
  12. Structure and mechanism of the glycyl radical enzyme pyruvate formate-lyase. Becker, A., Fritz-Wolf, K., Kabsch, W., Knappe, J., Schultz, S., Volker Wagner, A.F. Nat. Struct. Biol. (1999) [Pubmed]
  13. The anaerobic (class III) ribonucleotide reductase from Lactococcus lactis. Catalytic properties and allosteric regulation of the pure enzyme system. Torrents, E., Buist, G., Liu, A., Eliasson, R., Kok, J., Gibert, I., Gräslund, A., Reichard, P. J. Biol. Chem. (2000) [Pubmed]
  14. Gly-Gly-X, a novel consensus sequence for the proteolytic processing of viral and cellular proteins. López-Otín, C., Simón-Mateo, C., Martínez, L., Viñuela, E. J. Biol. Chem. (1989) [Pubmed]
  15. A model for transmembrane signalling by the aspartate receptor based on random-cassette mutagenesis and site-directed disulfide cross-linking. Maruyama, I.N., Mikawa, Y.G., Maruyama, H.I. J. Mol. Biol. (1995) [Pubmed]
  16. A novel polymorphism at codon 333 of human immunodeficiency virus type 1 reverse transcriptase can facilitate dual resistance to zidovudine and L-2',3'-dideoxy-3'-thiacytidine. Kemp, S.D., Shi, C., Bloor, S., Harrigan, P.R., Mellors, J.W., Larder, B.A. J. Virol. (1998) [Pubmed]
  17. Yeast and mammalian ras proteins have conserved biochemical properties. Temeles, G.L., Gibbs, J.B., D'Alonzo, J.S., Sigal, I.S., Scolnick, E.M. Nature (1985) [Pubmed]
  18. Phenotypic changes induced by a mutated ras gene during the development of Dictyostelium transformants. Reymond, C.D., Gomer, R.H., Nellen, W., Theibert, A., Devreotes, P., Firtel, R.A. Nature (1986) [Pubmed]
  19. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Yin, X.M., Oltvai, Z.N., Korsmeyer, S.J. Nature (1994) [Pubmed]
  20. A glycyl radical site in the crystal structure of a class III ribonucleotide reductase. Logan, D.T., Andersson, J., Sjöberg, B.M., Nordlund, P. Science (1999) [Pubmed]
  21. The mutations in Ashkenazi Jews with adult GM2 gangliosidosis, the adult form of Tay-Sachs disease. Navon, R., Proia, R.L. Science (1989) [Pubmed]
  22. Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Lin, S.C., Lin, C.R., Gukovsky, I., Lusis, A.J., Sawchenko, P.E., Rosenfeld, M.G. Nature (1993) [Pubmed]
  23. T lymphocyte recognition of peptide antigens: evidence favoring the formation of neoantigenic determinants. Thomas, D.W., Hoffman, M.D., Wilner, G.D. J. Exp. Med. (1982) [Pubmed]
  24. Human CD4(+) T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1. Münz, C., Bickham, K.L., Subklewe, M., Tsang, M.L., Chahroudi, A., Kurilla, M.G., Zhang, D., O'Donnell, M., Steinman, R.M. J. Exp. Med. (2000) [Pubmed]
  25. Arabidopsis thaliana GLN2-encoded glutamine synthetase is dual targeted to leaf mitochondria and chloroplasts. Taira, M., Valtersson, U., Burkhardt, B., Ludwig, R.A. Plant Cell (2004) [Pubmed]
  26. Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. Jurkat-Rott, K., Mitrovic, N., Hang, C., Kouzmekine, A., Iaizzo, P., Herzog, J., Lerche, H., Nicole, S., Vale-Santos, J., Chauveau, D., Fontaine, B., Lehmann-Horn, F. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  27. The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. Kirisako, T., Ichimura, Y., Okada, H., Kabeya, Y., Mizushima, N., Yoshimori, T., Ohsumi, M., Takao, T., Noda, T., Ohsumi, Y. J. Cell Biol. (2000) [Pubmed]
  28. Mutagenesis of the human apolipoprotein B gene in a yeast artificial chromosome reveals the site of attachment for apolipoprotein(a). McCormick, S.P., Ng, J.K., Taylor, S., Flynn, L.M., Hammer, R.E., Young, S.G. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  29. A peptide-hormone-inactivating endopeptidase in Xenopus laevis skin secretion. Carvalho, K.M., Joudiou, C., Boussetta, H., Leseney, A.M., Cohen, P. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  30. A single amino acid substitution (157 Gly----Val) in a phosphoglycerate kinase variant (PGK Shizuoka) associated with chronic hemolysis and myoglobinuria. Fujii, H., Kanno, H., Hirono, A., Shiomura, T., Miwa, S. Blood (1992) [Pubmed]
  31. Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia. Webster, M.K., Donoghue, D.J. EMBO J. (1996) [Pubmed]
  32. A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier. Komatsu, M., Chiba, T., Tatsumi, K., Iemura, S., Tanida, I., Okazaki, N., Ueno, T., Kominami, E., Natsume, T., Tanaka, K. EMBO J. (2004) [Pubmed]
  33. beta-subunits of Snf1 kinase are required for kinase function and substrate definition. Schmidt, M.C., McCartney, R.R. EMBO J. (2000) [Pubmed]
  34. Mutator phenotypes of yeast strains heterozygous for mutations in the MSH2 gene. Drotschmann, K., Clark, A.B., Tran, H.T., Resnick, M.A., Gordenin, D.A., Kunkel, T.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  35. Side chain contributions to the stability of alpha-helical structure in peptides. Lyu, P.C., Liff, M.I., Marky, L.A., Kallenbach, N.R. Science (1990) [Pubmed]
  36. Analysis of the substrate binding sites of human galactosyltransferase by protein engineering. Aoki, D., Appert, H.E., Johnson, D., Wong, S.S., Fukuda, M.N. EMBO J. (1990) [Pubmed]
  37. The role of proline 345 in diphtheria toxin translocation. Johnson, V.G., Nicholls, P.J., Habig, W.H., Youle, R.J. J. Biol. Chem. (1993) [Pubmed]
  38. Contribution to antibody-antigen interaction of structurally perturbed antigenic residues upon antibody binding. Tsumoto, K., Ueda, Y., Maenaka, K., Watanabe, K., Ogasahara, K., Yutani, K., Kumagai, I. J. Biol. Chem. (1994) [Pubmed]
  39. The anaerobic ribonucleotide reductase from Lactococcus lactis. Interactions between the two proteins NrdD and NrdG. Torrents, E., Eliasson, R., Wolpher, H., Gräslund, A., Reichard, P. J. Biol. Chem. (2001) [Pubmed]
 
WikiGenes - Universities