• 1
    Schilling S., Wasternack C., Demuth H.U. (2008) Glutaminyl cyclases from animals and plants: a case of functionally convergent protein evolution. Biol Chem;389:983991.
  • 2
    Abraham G.N., Podell D.N. (1981) Pyroglutamic acid. Non-metabolic formation, function in proteins and peptides, and characteristics of the enzymes effecting its removal. Mol Cell Biochem;38 Spec No:181190.
  • 3
    Goren H.J., Bauce L.G., Vale W. (1977) Forces and structural limitations of binding of thyrotrophin-releasing factor to the thyrotrophin-releasing receptor: the pyroglutamic acid moiety. Mol Pharmacol;13:606614.
  • 4
    Karten M.J., Rivier J.E. (1986) Gonadotropin-releasing hormone analog design. Structure-function studies toward the development of agonists and antagonists: rationale and perspective. Endocr Rev;7:4466.
  • 5
    Nillni E.A. (1999) Neuroregulation of ProTRH biosynthesis and processing. Endocrine;10:185199.
  • 6
    Friedman T.C., Loh Y.P., Cawley N.X., Birch N.P., Huang S.S., Jackson I.M., Nillni E.A. (1995) Processing of prothyrotropin-releasing hormone (Pro-TRH) by bovine intermediate lobe secretory vesicle membrane PC1 and PC2 enzymes. Endocrinology;136:44624472.
  • 7
    Pohl T., Zimmer M., Mugele K., Spiess J. (1991) Primary structure and functional expression of a glutaminyl cyclase. Proc Natl Acad Sci USA;88:1005910063.
  • 8
    Fischer W.H., Spiess J. (1987) Identification of a mammalian glutaminyl cyclase converting glutaminyl into pyroglutamyl peptides. Proc Natl Acad Sci USA;84:36283632.
  • 9
    Busby W.H.J., Quackenbush G.E., Humm J., Youngblood W.W., Kizer J.S. (1987) An enzyme(s) that converts glutaminyl-peptides into pyroglutamyl-peptides. Presence in pituitary, brain, adrenal medulla, and lymphocytes. J Biol Chem;262:85328536.
  • 10
    Schilling S., Appl T., Hoffmann T., Cynis H., Schulz K., Jagla W., Friedrich D., Wermann M., Buchholz M., Heiser U., von Horsten S., Demuth H.U. (2008) Inhibition of glutaminyl cyclase prevents pGlu-Abeta formation after intracortical/hippocampal microinjection in vivo/in situ. J Neurochem;106:12251236.
  • 11
    Schilling S., Hoffmann T., Manhart S., Hoffmann M., Demuth H.U. (2004) Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions. FEBS Lett;563:191196.
  • 12
    D’Arrigo C., Tabaton M., Perico A. (2009) N-terminal truncated pyroglutamyl beta amyloid peptide Abetapy3-42 shows a faster aggregation kinetics than the full-length Abeta1-42. Biopolymers;91:861873.
  • 13
    Schlenzig D., Manhart S., Cinar Y., Kleinschmidt M., Hause G., Willbold D., Funke S.A., Schilling S., Demuth H.U. (2009) Pyroglutamate formation influences solubility and amyloidogenicity of amyloid peptides. Biochemistry;48:70727078.
  • 14
    Cynis H., Scheel E., Saido T.C., Schilling S., Demuth H.U. (2008) Amyloidogenic processing of amyloid precursor protein: evidence of a pivotal role of glutaminyl cyclase in generation of pyroglutamate-modified amyloid-beta. Biochemistry;47:74057413.
  • 15
    Schilling S., Lauber T., Schaupp M., Manhart S., Scheel E., Bohm G., Demuth H.U. (2006) On the seeding and oligomerization of pGlu-amyloid peptides (in vitro). Biochemistry;45:1239312399.
  • 16
    He W., Barrow C.J. (1999) The A beta 3-pyroglutamyl and 11-pyroglutamyl peptides found in senile plaque have greater beta-sheet forming and aggregation propensities in vitro than full-length A beta. Biochemistry;38:1087110877.
  • 17
    Saido T.C. (1998) Alzheimer’s disease as proteolytic disorders: anabolism and catabolism of beta-amyloid. Neurobiol Aging;19:S69S75.
  • 18
    Schilling S., Zeitschel U., Hoffmann T., Heiser U., Francke M., Kehlen A., Holzer M. et al. (2008) Glutaminyl cyclase inhibition attenuates pyroglutamate Abeta and Alzheimer’s disease-like pathology. Nat Med;14:11061111.
  • 19
    Cynis H., Schilling S., Bodnar M., Hoffmann T., Heiser U., Saido T.C., Demuth H.U. (2006) Inhibition of glutaminyl cyclase alters pyroglutamate formation in mammalian cells. Biochim Biophys Acta;1764:16181625.
  • 20
    Buchholz M., Heiser U., Schilling S., Niestroj A.J., Zunkel K., Demuth H.U. (2006) The first potent inhibitors for human glutaminyl cyclase: synthesis and structure-activity relationship. J Med Chem;49:664677.
  • 21
    Buchholz M., Hamann A., Aust S., Brandt W., Bohme L., Hoffmann T., Schilling S., Demuth H.U., Heiser U. (2009) Inhibitors for human glutaminyl cyclase by structure based design and bioisosteric replacement. J Med Chem;52:70697080.
  • 22
    Schilling S., Niestroj A.J., Rahfeld J.-U., Hoffmann T., Wermann M., Zunkel K., Wasternack C., Demuth H.U. (2003) Identification of human glutaminyl cyclase as a metalloenzyme: inhibition by imidazole derivatives and heterocyclic chelators. J Biol Chem;278:4977349779.
  • 23
    Schilling S., Hoffmann T., Rosche F., Manhart S., Wasternack C., Demuth H.U. (2002) Heterologous expression and characterization of human glutaminyl cyclase: evidence for a disulfide bond with importance for catalytic activity. Biochemistry;41:1084910857.
  • 24
    Schilling S., Hoffmann T., Wermann M., Heiser U., Wasternack C., Demuth H.U. (2002) Continuous spectrometric assays for glutaminyl cyclase activity. Anal Biochem;303:4956.
  • 25
    Huang K.F., Liaw S.S., Huang W.L., Chia C.Y., Lo Y.C., Chen Y.L., Wang A.H. (2011) Structures of human Golgi-resident glutaminyl cyclase and its complexes with inhibitors reveal a large loop movement upon inhibitor binding. J Biol Chem;286:1243912449.
  • 26
    Ruiz-Carrillo D., Koch B., Parthier C., Wermann M., Dambe T., Buchholz M., Ludwig H.H., Heiser U., Rahfeld J.U., Stubbs M.T., Schilling S., Demuth H.U. (2011) Structures of glycosylated mammalian glutaminyl cyclases reveal conformational variability near the active center. Biochemistry;50:62806288.
  • 27
    Schilling S., Cynis H., von Bohlen A., Hoffmann T., Wermann M., Heiser U., Buchholz M., Zunkel K., Demuth H.U. (2005) Isolation, catalytic properties, and competitive inhibitors of the zinc-dependent murine glutaminyl cyclase. Biochemistry;44:1341513424.
  • 28
    Schilling S., Lindner C., Koch B., Wermann M., Rahfeld J.U., Bohlen A.V., Rudolph T., Reuter G., Demuth H.U. (2007) Isolation and characterization of glutaminyl cyclases from drosophila: evidence for enzyme forms with different subcellular localization. Biochemistry;38:1092110930.
  • 29
    Calvaresi M., Garavelli M., Bottoni A. (2008) Computational evidence for the catalytic mechanism of glutaminyl cyclase. A DFT investigation. Proteins;3:527538.
  • 30
    Cynis H., Hoffmann T., Friedrich D., Kehlen A., Gans K., Kleinschmidt M., Rahfeld J.U. et al. (2011) The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions. EMBO Mol Med;3:545558.