• 제목/요약/키워드: S-adenosyl-$_L$-homocysteine

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A synthesis of sugar-modified S-adenosyl-L-homocysteine(AdoHcy) analogues as inhibitors of AdoHcy hydrolase via the coupling sugar-modified adenosine analogues with L-homocysteine sodium salt.

  • Kim, Beom-Tae;Kim, Seung-Ki;Ryu, Jeong-Hyun;Hwang, Ki-Jun
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.235.3-236
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    • 2003
  • S-adenosyl-L-homocysteine(AdoHcy) is the product of all biological methylation in which S-adenosyl-L-methionine (AdoMet) is utilized as a methyl donor and is reversibly hydrolyzed to L-homocysteine and adenosine by AdoHcy hydrolase physiologically. Inhibition of this enzyme results in intracelluar accumulation of AdoHcy leading to a feedback inhibition of AdoMet-dependent methylation reactions which are essential for viral replication. (omitted)

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국화 기형화 발생과 S-adenosyl-L-homocysteine hydrolase 유전자 발현 (S-adenosyl-L-homocysteine hydrolase gene is down-regulated in abnormal flower inducing environment in chyrsanthemum)

  • 허은주;박상근;임진희;최성열;이영란
    • 화훼연구
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    • 제18권4호
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    • pp.278-283
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    • 2010
  • 본 시험은 국화에서의 기형화 발생과 DNA 메틸레이션에 관여하는 S-adenosyl-L-homocysteine hydrolase (SAHH) 유전자 발현과의 관련성을 검토하기 위해 수행하였다. 스프레이 국화 'Lerbin'은 단일후 14일에서 27일 사이에 고온과 장일 조건에서 기형화가 발생되어, $35/20^{\circ}C$의 고온과 14시간의 장일 처리 할 경우 $25/20^{\circ}C$(12 h/12 h)에 비해 설상화가 2배 이상 증가하는 양상을 보였다. 스프레이 국화 'Lerbin'에서 분리한 전장 cDNA (DgSAHH)는 크기가 1455 bp로 다른 작물과 90%이상의 높은 상동성을 나타내었다. 국화의 DgSAHH 유전자 발현은 기형화 발생을 유도하는 고온과 장일 조건에서 크게 감소하였다. 이러한 결과를 통해 국화의 화아 발달에 있어서 DgSAHH 유전자 발현은 온도와 일장의 영향을 받으며, 억제된 이 유전자의 발현이 기형화 발생에 관여할 수 있을 것으로 판단된다.

S-Adenosyl-L-Methionine Analogues to Enhance the Production of Actinorhodin

  • Chong You-Hoon;Young Jung-Mo;Kim Jin-Young;Lee Yu-Kyung;Park Kwang-Su;Cho Jun-Ho;Kwon Hyung-Jin;Suh Joo-WOn;Lim Yoong-Ho
    • Journal of Microbiology and Biotechnology
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    • 제16권7호
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    • pp.1154-1157
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    • 2006
  • It is known that overexpression of S-adenosyl-L-methionine (SAM) synthetase or exogenous addition of SAM enhances the production of actinorhodin, one of pigmented antibiotics found from Streptomyces coelicolor. In order to discover a novel compound as a signal molecule to produce actinorhodin instead of SAM, several compounds were synthesized based on the relationships between structures of the SAM analogues and their actinorhodin productivities. Of these, a few compounds showed better productivities of actinorhodin than SAM.

돼지 췌장내 Protein Methylase I의 분리정제 및 성질 (Purification and Properties of Protein Methylase I from Hog Pancreas)

  • 이향우;장만식
    • 약학회지
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    • 제31권3호
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    • pp.173-181
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    • 1987
  • Protein methylase I has been partially purified from hog pancreas with a 11% yeild. The final preparation is completely free of any other protein-specific methyltransferases and endogenous substrate proteins. The enzyme has an optimum pH of 7.2 and the approximate molecular weight is above 800 thousands dalton. The Km values for S-adenosyl-L-methionine and histone type II-A are 1.32$\times$10$^{-5}$M. The Ki value for S-adenosyl-L-homocysteine is 1.52$\times$10$^{-6}$M. The effect of enyzme concentration on the activity showed a slight sigmoidal curve suggesting the involvement of certain cofactors. Even though the purified enzyme showed two bands on polyacrylamide gel electrophoresis, the enzyme is highly specific for the arginine residues of protein and specifically, highly specific for histone, suggesting histonespecific protein methylase I.

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In vitro Translation and Methylation of Iso-1-Cytochrome C from Saccharomyces Cerevisiae

  • Paik, Woon-Ki;Park, Kwang-Sook;Tuck, Martin;Kim, Sang-Duk
    • 한국미생물생명공학회:학술대회논문집
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    • 한국미생물생명공학회 1986년도 추계학술대회
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    • pp.505.1-505
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    • 1986
  • The gene for iso-1-cytochrome c for Saccharomyces cerevisiae was recloned into a pSP65 vector containing an active bacteriophage SP6 promoter. The iso-1-cytochrome c gene was cloned as an 856 bp Xho 1-Hind III fragment. When the resulting plasmid was digested at the Hind 111 site 279 bases downstream from the termination codon of the gene and transcribed in vitro using SP6 RNA polymerase, full length transcripts were produced. The SP6 iso-1-cytochrome c mRNA was translated using a rabbit reticulocyte lysate system and the protein products analyzed on SDS polyacrylamide gels. One major band was detected by autofluorography. This band was found to have a molecular weight of 12,000 Da and coincided with the Coomassie staining band of apocytochrome c from S. cerebisiae. The product was also shown to be identical with that of standard yeast apocytochrome c on an isoelectric focusing gel. The in vitro synthesized iso-a-cytochrome c was methylated by adding partially purified S-adenosyl-L-methionine . protein-lysine N-methyltransferase (Protein methylase III; EC 2.1.1.43) from S. cerevisiae along with S-adenosyl-L-methionine to the in vitro translation mixtures. The methylation was shown to be inhibited by the addition of the methylase inhibitor S-adenosyl-L-homocysteine or the protein synthesis inhibitor pu omycin. The methyl derivatives in the protein were identified as $\varepsilon$-N-mono, di and trimethyllysine by amino acid analysis. The molar ratio of methyl groups incorporated to that of cytochrome c molecules synthesized showed that 23% of the translated cytochrome c molecules were methylated by protein methylase III.

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CRYSTAL STRUCTURE OF tRNA ($m^1$ G37) METHYLTRANSFERASE

  • Ahn, Hyung-Jun;Lee, Byung-Ill;Yoon, Hye-Jin;Yang, Jin-Kuk;Suh, Se-Won
    • 한국결정학회:학술대회논문집
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    • 한국결정학회 2003년도 춘계학술연구발표회
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    • pp.17-17
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    • 2003
  • tRNA (m¹ G37) methyltransferase (TrmD) catalyze s the trans for of a methyl group from S-adenosyl-L-methionine (AdoMet) to G/sup 37/ within a subset of bacterial tRNA species, which have a residue G at 36th position. The modified guanosine is adjacent to and 3' of the anticodon and is essential for the maintenance of the correct reading frame during translation. We have determined the first crystal structure of TrmD from Haemophilus influenzae, as a binary complex with either AdoMet or S-adenosyl-L-homocysteine (AdoHcy), as a ternary complex with AdoHcy/phosphate, and as an apo form. The structure indicates that TrmD functions as a dimer (Figure 1). It also suggests the binding mode of G/sup 36/G/sup 37/ in the active site of TrmD and catalytic mechanism. The N-terminal domain has a trefoil knot, in which AdoMet or AdoHcy is bound in a novel, bent conformation. The C-terminal domain shows a structural similarity to DNA binding domain of trp or tot repressor. We propose a plausible model for the TrmD₂-tRNA₂ complex, which provides insights into recognition of the general tRNA structure by TrmD (Figure 2).

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Farnesylcysteine Methyltransferase Activity and Ras Protein Expression in Human Stomach Tumor Tissue

  • Han, Eui-Sik;Oh, Hye-Young;Ha, Kwang-Won;Han, Beom-Seok;Hong, Seok-Min;Han, Jung-Whwan;Hong, Sung-Youl;Noh, Sung-Hun;Lee, Hyang-Woo
    • Archives of Pharmacal Research
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    • 제21권4호
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    • pp.378-384
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    • 1998
  • The processing pathway of G-proteins and Ras family proteins includes the isoprenylation of the cysteine residue, followed by proteolysis of three terminal residues and .alpha.-carboxyl methyl esterification of the cysteine residue. Farnesylcysteine methyltransferase (FCMT) activity is responsible for the methylation reaction which play a role in the membrane attachment of a variety of cellular proteins. Four kinds of Ras protein (c-Ha-ras, c-N-Ras, c-Ki-Ras, pan-Ras) expression were detected in adenocarcinoma of human tissue by immunohistochemical method, and hematoxylin and eosin staining. The level of Ras protein in human stomach tumor tissues was much higher than in normal and peritumoral regions of the same biopsy samples. The FCMT activities of each cellular fractions were high in mitochondrial fraction followed by microsomal fraction, whole homogenate and cytosolic fraction. The inhibitory effect on FCMT activity on stomach tumor tissue was determined after treatment with 0.25 $\mu\textrm{M}$ of S-adenosyl-$_L$-homocysteine. S-adenosyl-$_L$-homocysteine inhibited FCMT activity from 11.2% to 30.5%. These results suggested that FCMT might be involved in Ras proteins activity.

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Purification and Characterization of Protein Methylase II from Porcine Testis

  • Jung, Ki-Kyung;Kwon, Myung-Hee;Lee, Hoi-Young;Lee, Hyang-Woo;Hong, Sung-Youl
    • BMB Reports
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    • 제28권2호
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    • pp.149-154
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    • 1995
  • Protein methylase II (S-adenosyl-L-methionine : protein O-methyl-transferase, EC 2.1.1.24; PM II) was purified approximately 1250-fold from porcine testis by fractional precipitation and DEAE-cellulose chromatography, followed by gel filtration on a Sephadex G-75 column and HPLC on a Protein Pak 125 column. The molecular weight of the enzyme was estimated to be 33,000 daltons by SDS-PAGE, which agreed with the value determined by gel filtration. Isoelectric focusing of purified PM II showed a single protein species with an isoelectric point of 6.2. The optimum pH for the reaction was 6.0. The $K_m$ value of the enzyme was $1{\times}10^{-5}M$ with a $V_{max}$ value of 769 pmol/min/mg of enzyme. S-adenosyl-L-homocysteine is a competitive inhibitor of PM II with a $K_i$ value of $1.38{\times}10^{-6}M$.

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Development of Mechanism-based Irreversible Inhibitors of S-Adenosylhomocysteine Hydrolase as Borad-spectrum Antiviral Agents

  • Lee, Kang-Man;Moon, Hyung-Ryong;Choi, Won-Jun;Park, Jae-Gyu;Shin, Dae-Hong;Jeong, Lak-Shin
    • 대한약학회:학술대회논문집
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    • 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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    • pp.186-190
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    • 2002
  • S- Adenosylhomocysteine hydrolase $(SAH)^1$ catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L-homocysteine. Inhibition of this enzyme accumulates S-adenosylhomocysteine, which in turn inhibits S-adenosyl-L-methionine dependent transmethylation, resulting in no formation of the capped methylated structure at the 5'-terminus of viral mRNA. Thus, S-adenosylhomocysteine hydrolase has been an attractive target for the development of broad spectrum of antiviral agents. (omitted)

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