High Molecular Weight Transglutaminase Inhibitor Produced by a Microorganism (Streptomyces lavendulae Y-200)

Transglutaminases catalyze the cross-linking and amine incorporation of proteins, and are implicated in various biological phenomena such as blood clotting, wound healing, apoptosis, and cell differentiation. Streptomyces lavendulae Y-200, isolated from soil, produced a substance that inhibited transglutaminases. The inhibitory substance was purified from the cultured medium by procedures of acid precipitation, deoxyribonuclease treatment, and gel filtration chromatography. The partially purified sample was dark brown. The inhibitory activity was stable under acidic, alkaline, and high temperature conditions, and resistant to the treatment with proteinases such as trypsin and Pronase. The molecular weight of the inhibitory substance was estimated to be between 104 and 105 from its permeability through ultrafilter membranes. The acid hydrolysate of the inhibitory substance contained amino acids and sugars. The inhibitory substance inhibited both calcium-dependent and calcium-independent transglutaminases in a competitive manner with a glutamine substrate. The extent of inhibition caused by the calcium-dependent transglutaminase increased with increasing calcium concentration. The results obtained here may help identify a novel regulatory substance of transglutaminase in biological systems.

[1]  W. Strittmatter,et al.  Pathogenesis of Inclusion Bodies in (CAG)n/Qn‐Expansion Diseases with Special Reference to the Role of Tissue Transglutaminase and to Selective Vulnerability , 1999, Journal of neurochemistry.

[2]  L. Lorand,et al.  Neurodegenerative diseases and transglutaminase. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. Sasaki,et al.  Analysis of catalytic action of transglutaminase induced in human promyelocytic leukemia (HL-60) and human hepatoblastoma (HepG2) cells. , 1996, Bioscience, biotechnology, and biochemistry.

[4]  A. Stern,et al.  Transglutaminase inhibition by 2-[(2-oxopropyl)thio]imidazolium derivatives: mechanism of factor XIIIa inactivation. , 1994, Biochemistry.

[5]  R. Graham,et al.  Gh: a GTP-binding protein with transglutaminase activity and receptor signaling function. , 1994, Science.

[6]  M. Paulsson,et al.  Transglutaminases: Protein Cross-Linking Enzymes in Tissues and Body Fluids , 1994, Thrombosis and Haemostasis.

[7]  M. Chedekel,et al.  Melanin standard method: empirical formula. , 1992, Pigment cell research.

[8]  L. Dini,et al.  In vivo and in vitro induction of 'tissue' transglutaminase in rat hepatocytes by retinoic acid. , 1992, Biochimica et biophysica acta.

[9]  R. Rice,et al.  Transglutaminases: multifunctional cross‐linking enzymes that stabilize tissues , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  I. Kato,et al.  Analysis by High-performance Anion-exchange Chromatography of Component Sugars as Their Fluorescent Pyridylamino Derivatives , 1991 .

[11]  S. -. Park,et al.  Protransglutaminase E from guinea pig skin. Isolation and partial characterization. , 1990, The Journal of biological chemistry.

[12]  A. Matsuura,et al.  Purification and Characteristics of a Novel Transglutaminase Derived from Microorganisms , 1989 .

[13]  T. Bjornsson,et al.  Bovine aortic endothelial cell transglutaminase. Enzyme characterization and regulation of activity. , 1989, The Biochemical journal.

[14]  M. Piacentini,et al.  Apoptotic hepatocytes become insoluble in detergents and chaotropic agents as a result of transglutaminase action , 1989, FEBS letters.

[15]  A. Krantz,et al.  Synthesis, chemistry, and absolute configuration of novel transglutaminase inhibitors containing a 3-halo-4,5-dihydroisoxazole , 1988 .

[16]  L. Fésüs,et al.  Searching for the function of tissue transglutaminase: its possible involvement in the biochemical pathway of programmed cell death. , 1988, Advances in experimental medicine and biology.

[17]  A. Falus,et al.  Induction and activation of tissue transglutaminase during programmed cell death , 1987, FEBS letters.

[18]  C. Bergamini,et al.  Inhibition of erythrocyte transglutaminase by GTP. , 1987, Biochimica et biophysica acta.

[19]  A. McDermott,et al.  Photosystem I charge separation in the absence of center A and B. III. Biochemical characterization of a reaction center particle containing P-700 and FX , 1987 .

[20]  K. Achyuthan,et al.  Identification of a guanosine triphosphate-binding site on guinea pig liver transglutaminase. Role of GTP and calcium ions in modulating activity. , 1987, The Journal of biological chemistry.

[21]  B. Bernard,et al.  Precocious appearance of involucrin and epidermal transglutaminase during differentiation of psoriatic skin , 1986, The British journal of dermatology.

[22]  R. Sasaki,et al.  One-step Purification of Guinea Pig Liver Transglutaminase Using a Monoclonal-antibody Immunoadsorbent , 1985 .

[23]  S. I. Chung,et al.  Development of selective inhibitors of transglutaminase. Phenylthiourea derivatives. , 1985, The Journal of biological chemistry.

[24]  J. Delcros,et al.  The competitive inhibition of tissue transglutaminase by α‐difluoromethylornithine , 1984 .

[25]  S. Ballaron,et al.  Transglutaminase activity in human and rabbit ear comedogenesis: a histochemical study. , 1984, The Journal of investigative dermatology.

[26]  M. Murtaugh,et al.  Induction of tissue transglutaminase in human peripheral blood monocytes , 1984, The Journal of experimental medicine.

[27]  H. Yonekawa,et al.  Participation of the microsomal electron transport system in mutagenic activation of 4-dimethylaminoazobenzene, 4-methylaminoazobenzene and their 3'-methyl-derivatives. , 1982, Biochemical and biophysical research communications.

[28]  R. Kannagi,et al.  Transglutaminase activity during the differentiation of macrophages. , 1982, Biochemical and biophysical research communications.

[29]  L. Fésüs.  Transglutaminase activation: Significance with respect to immunologic phenomena , 1982, Survey of immunologic research.

[30]  H. A. Carter,et al.  Increase in proliferative markers after inhibition of transglutaminase. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[31]  P. Azari,et al.  Transglutaminase activity in normal and hereditary cataractous rat lens and its partial purification. , 1981, Current eye research.

[32]  P. J. Birckbichler,et al.  CELLULAR TRANSGLUTAMINASE, GROWTH, AND TRANSFORMATION , 1978, Annals of the New York Academy of Sciences.

[33]  J. Finlayson,et al.  The ɛ-(γ-Glutamyl)Lysine Crosslink and the Catalytic Role of Transglutaminases , 1977 .

[34]  J. E. Folk,et al.  Alkyl isocyanates as active site-directed inactivators of guinea pig liver transglutaminase. , 1975, The Journal of biological chemistry.

[35]  L. Lorand,et al.  A filter paper assay for transamidating enzymes using radioactive amine substrates. , 1972, Analytical biochemistry.

[36]  Y. Mikami,et al.  Chromogenicity of Streptomyces , 1972, Applied microbiology.

[37]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[38]  J. E. Folk.  [127] Transglutaminase (guinea pig liver) , 1970 .

[39]  T. Mcmeekin,et al.  Separation of α-, β- and γ-Casein , 1952 .