• Title/Summary/Keyword: glnK

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Structural Characterization of Mouse HAUSP, a Proteolysis Regulator of p53

  • Lee, Hye-Jin;Yoo, Kyong-Jai;Baek, Kwang-Hyun
    • Animal cells and systems
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    • v.8 no.3
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    • pp.205-212
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    • 2004
  • The tumor suppressor protein p53 is stabilized by the herpes-virus-associated ubiquitin-specific protease (HAUSP), a deubiquitinating enzyme. We previously isolated and characterized a mouse orthologue of HAUSP, mHAUSP. mHAUSP cDNA consisted of 3,312 bp encodes 1,103 amino acids with a molecular weight of approximately 135 kDa containing highly conserved Cys, Asp (I), His, and Asn/Asp (II) domains. In this study, we carried out site-directed mutagenesis of 6 conserved amino acids (Cys224, Gln231, Asp296, His457, His465, and Asp482) in Cys box, QQD box, and His box. Interestingly, the conserved Gln 231 was not essential for the catalytic activity of mHAUSP. However, the other conserved amino acids were required for deubiquitinating activity of mHAUSP. We performed isopeptidase assay and confirmed that mHAUSP is able to remove ubiquitin from ubiquitinated substrates. In addition, we observed that mHAUSP induces apoptosis in HeLa cells.

Predictive Value of XRCC1 and XRCC3 Gene Polymorphisms for Risk of Ovarian Cancer Death After Chemotherapy

  • Cheng, Chun-Xia;Xue, Min;Li, Kai;Li, Wu-Sheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2541-2545
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    • 2012
  • Objective: To investigate any association between XRCC1 and XRCC3 polymorphisms and outcome of platinum-based chemotherapy in ovarian cancer patients. Methods: With a prospective study design was cases were consecutively collected from January 2005 to January 2007. All 310 included patients were followed-up until the end of January 2010. Genotyping of XRCC1 and XRCC3 polymorphisms was conducted by TaqMan Gene Expression assays. Results: A total of 191 patients died during follow-up. Our study showed a lower survival rate in XRCC1 399 Arg/Arg genotype than Gln/Gln, with a significant increased risk of death (HR=1.69, 95%CI=1.07-2.78). Similarly, those carrying XRCC3 Thr/Thr genotype had a increased risk as compare to the Met/Met genotype, with a HR (95% CI) of 1.90 (1.12-3.41). There was no significant association between XRCC1 Arg194Trp and XRCC1Arg280His gene polymorphisms and ovarian cancer death. Conclusion: Our study demonstrates that polymorphisms in DNA repair genes have roles in the susceptibility and survival of ovarian cancer patients.

Computational Analysis of Human Chemokine Receptor Type 6

  • Sridharan, Sindhiya;Saifullah, Ayesha Zainab;Nagarajan, Santhosh Kumar;Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.11 no.2
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    • pp.121-129
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    • 2018
  • CXCR6 is a major target in drug design as it is a determinant receptor in many diseases like AIDS, Type I Diabetes, some cancer types, atherosclerosis, tumor formation, liver disease and steatohepatitis. In this study, we propose the active site residues of CXCR6 molecule. We employed homology modelling and molecular docking approach to generate the 3D structure for CXCR6 and to explore its interaction between the antagonists and agonists. 3D models were generated using 14 different templates having high sequence identity with CXCR6. Surflex docking studies using pyridine and pyrimidine derivatives enabled the analysis of the binding site and finding of the important residues involved in binding. 3D structure of CXCL16, a natural ligand for CXCR6, was modelled using PHYRE and protein - protein docking was performed using ClusPro. The residues which were found to be crucial in interaction with the ligand are THR110, PHE113, TYR114, GLN160, GLN195, CYS251 and SER255. This study can be used as a guide for therapeutic studies of human CXCR6.

Angiotensin-Converting Enzyme Inhibitory Activity of Enzymatic Hydrolysates of Crassostrea gigas (Oyster) (굴 효소 가수분해물의 angiotensin converting enzyme 저해작용)

  • Do, Hyung-Joo;Park, Hye-Jin;Kim, Ok-Ju;Kim, Andre;Choi, Yeung-Joon;Choung, Se-Young;Ha, Jong-Myung
    • Journal of Life Science
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    • v.22 no.2
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    • pp.220-225
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    • 2012
  • The peptides of enzymatic hydrolysates from oyster were determined by inhibitory activity against angiotensin-converting enzyme. The ACE inhibitory activity of enzymatic oyster hydrolysates increases with hydrolysis time. Among enzymatic oyster hydrolysates, oyster hydrolysates incubated with Protamex showed the best ACE inhibitory activity after 10 h. Hydrolysates were filtered through a HiSep ultrafiltration membrane (M.W. cut-off 30 kDa, 10 kDa) to obtain the peptide fractions with ACE inhibition activity. These fractions were applied to an HPLC column (watchers 120 ODS-AP $250{\times}4.6$ ($5{\mu}m$)). Six active fractions were collected and the range of ACE inhibition was from 29.56 to 85.85%. Peptide was purified from fraction B, showing the highest ACE inhibitory activity, and its sequence was Leu-Gln-Pro. These results suggest that PEH may be beneficial for developing antihypertensive food and drug.

Purification and Characterization of Fibrinolytic Enzyme from Lepista nuda (민자주방망이버섯으로부터 혈전용해효소의 정제 및 특성 연구)

  • Kim, Jun-Ho
    • The Korean Journal of Mycology
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    • v.33 no.2
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    • pp.69-74
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    • 2005
  • Fibrinolytic enzyme has been isolated and purified from the edible mushroom, Lepista nuda. The apparent molecular mass of purified enzyme was estimated to be 34 KDa by SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of the enzyme was Tyr-Pro-Ser-Pro-Ser-His-Gln-Thr-Ala-Val-Asn-Ala-Ile-Ile-X. It has a pH optimum at $7.0.{\sim}9.5$, suggesting that the purified enzyme is an alkaline protease. It shows the maximum fibrinolytic activity at $55^{\circ}C$. The fibrinolytic activity was inhibited by phenylmethylsulfonyl fluoride, indicating that the purified enzyme is a serine protease. The activity of the purified enzyme was totally inhibited by $Hg^{2+}$.

Effects of Dietary Glutamine and Glutamate Supplementation on Small Intestinal Structure, Active Absorption and DNA, RNA Concentrations in Skeletal Muscle Tissue of Weaned Piglets during d 28 to 42 of Age

  • Liu, Tao;Peng, Jian;Xiong, Yuanzhu;Zhou, Shiqi;Cheng, Xuehui
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.2
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    • pp.238-242
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    • 2002
  • Seventy-four piglets were used to investigate the effects of dietary glutamine (Gln) and glutamate (Glu) on the mucosal structure and active absorption of small intestinal, DNA and RNA concentrations of skeletal muscle tissue in piglets during d 28 to 42 of age. Postweaning piglets were fed for 14 d corn- and soybean meal-based diets supplemented with 0.0 or 1.0% L-Gln or L-Glu. On d 7 and 14 postweaning, pigs' small intestinal sections and longissimus dorsi were collected, at the same time, the D-xylose absorption test was conducted. The results suggested that in comparison to control piglets, jejunal atrophy during the first week postweaning was prevented by the glutamine and glutamate supplementation (1%) and the capability of small intestine to absorb Dxylose was improved. Furthermore the RNA concentration in skeletal muscle tissue was increased. These results provide an experimental basis for use of glutamine and glutamate on alleviating the weaning stresses and improving piglets' growth performance.

Identification of a novel mutation in a patient with pseudohypoparathyroidism type Ia

  • Lee, Ye Seung;Kim, Hui Kwon;Kim, Hye Rim;Lee, Jong Yoon;Choi, Joong Wan;Bae, Eun Ju;Oh, Phil Soo;Park, Won Il;Ki, Chang Seok;Lee, Hong Jin
    • Clinical and Experimental Pediatrics
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    • v.57 no.5
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    • pp.240-244
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    • 2014
  • Pseudohypoparathyroidism type Ia (PHP Ia) is a disorder characterized by multiform hormonal resistance including parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO). It is caused by heterozygous inactivating mutations within the Gs alpha-encoding GNAS exons. A 9-year-old boy presented with clinical and laboratory abnormalities including hypocalcemia, hyperphosphatemia, PTH resistance, multihormone resistance and AHO (round face, short stature, obesity, brachydactyly and osteoma cutis) which were typical of PHP Ia. He had a history of repeated convulsive episodes that started from the age of 2 months. A cranial computed tomography scan showed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicated mild mental retardation. Family history revealed that the patient's maternal relatives, including his grandmother and 2 of his mother's siblings, had features suggestive of AHO. Sequencing of the GNAS gene of the patient identified a heterozygous nonsense mutation within exon 11 (c.637 C>T). The C>T transversion results in an amino acid substitution from Gln to stop codon at codon 213 ($p.Gln213^*$). To our knowledge, this is a novel mutation in GNAS.

Purification and Characterization of Substance P-related Peptide from the Body of the African Lungfish, Protopterus dolloi

  • Kim, Chan-Hee;Kim, Eun-Jung;Go, Hye-Jin;Lee, Hyung-Ho;Hong, Yong-Ki;Kim, Hyung-Rak;Chung, Joon-Ki;Park, Jang-Su;Muneoka, Yojiro;Park, Nam-Gyu
    • Bulletin of the Korean Chemical Society
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    • v.27 no.7
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    • pp.1015-1019
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    • 2006
  • The peptide with structural similarity to mammalian substance P (M-SP) has been isolated from extract of the body of the African lungfish, Protopterus dolloi, using the rectum of the newt as the bioassay system. The primary structure of the SP-related peptide was identified as Lys-Pro-Arg-Pro-Asp-Gln-Phe-Tyr-Gly-Leu-Met-NH2 (L-SP) and contained four substitutions ($Lys^{1}\rightarrow $ Arg, $Arg^{3}\rightarrow$ Lys, $Asp^{5}\rightarrow$ Gln, and $Tyr^{8}\rightarrow$ Phe) compared with M-SP; this structure is identical to that of the peptide isolated from the gut of the Australian lungfish. Circular dichroism spectra showed that L-SP had an unordered structure in the buffer solution and phospholipid bilayers. This peptide was found to have an excitatory effect on rectal muscle tissues of newt, quail, and fish. L-SP also had a more potent vasodilatory effect on the guinea-pig aorta than that of M-SP. The identification of the peptide provides evidence that SP family, hitherto confined to mammals, have a widespread occurrence in lungfish.

UV-spectrophotometric and electrophoretic analysis composition of protein and the content of sugars of young Ricinus communis L. by cold treatment (UV-분광광도법과 전기영동에 의한 피마자 유식물에서 저온처리에 의한 당류 함량과 단백질 구성의 분석)

  • Cho, Bong-Heuy;Park, Sun Young;Park, Myon-Yong
    • Analytical Science and Technology
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    • v.8 no.2
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    • pp.181-186
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    • 1995
  • The contents of sucrose and reducing sugars of cotyledons and hypocotyls of Ricinus communis L were increased slightly during cold treatment at $4^{\circ}C$. The concentration of total amino acids was increased continuosly during cold treatment. But the contents of hydrophilic amino acids, Asp/Asn, Glu/Gln, Thr, Ser, Ala and cationic amino acids, Arg and Lys were varied dramatically with the cold treated time. The cold treatment induced 24, 52, 54, 55, 56 and 73.5kD of proteins in cotyledons and 55, 56 and 73.5kD of proteins in hypocotyls. 24, 42, 49 and 52kD of proteins in cotyledons and hypocotyls were boiling stable. They were not denatrated by boiling at $100^{\circ}C$.

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Relationship Between Antimetabolite Toxicity and Pharmacogenetics in Turkish Cancer Patients

  • Dogan, Mutlu;Karabulut, Halil G.;Tukun, Ajlan;Demirkazik, Ahmet;Utkan, Gungor;Yalcin, Bulent;Dincol, Dilek;Akbulut, Hakan;Icli, Fikri
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1553-1556
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    • 2012
  • Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. Patients and Methods: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms. Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. Conclusion: Pharmacogenetics might contribute to tailored therapy.