• Biomolecules & Therapeutics
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• 제25권1호
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• pp.4-11
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• 2017

Heterotrimeric G proteins are key intracellular coordinators that receive signals from cells through activation of cognate G protein-coupled receptors (GPCRs). The details of their atomic interactions and structural mechanisms have been described by many biochemical and biophysical studies. Specifically, a framework for understanding conformational changes in the receptor upon ligand binding and associated G protein activation was provided by description of the crystal structure of the ${\beta}2$-adrenoceptor-Gs complex in 2011. This review focused on recent findings in the conformational dynamics of G proteins and GPCRs during activation processes.

• 한국자기공명학회논문지
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• 제16권1호
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• pp.67-77
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• 2012

The small molecule binding to the c-Jun N-terminal kinase 3 (JNK3) was examined by the measurements of saturation transfer difference (STD) NMR experiments. The STD NMR experiment of ATP added to JNK3 clearly showed the binding of the nucleotide to the kinase. The STD NMR spectrum of dNTPs added to JNK3 discriminated the kinase-bound nucleotide from the unbound ones. After the five-fold addition of ATP to the dNTPs and JNK3 mixture, only signals of the cognate substrate of JNK3, ATP, were observed from the STD NMR experiment. These results signify that by the STD NMR the small molecules bound to JNK3 can be discriminated from the pool of the unbound molecules. Furthermore the binding mode of the small molecule to JNK3 can be determined by the competition experiments with ATP.

• BMB Reports
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• 제31권6호
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• pp.525-535
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• 1998

A critical step in the faithful translation of genetic information is specific tRNA recognition by aminoacyl-tRNA synthetases. These enzymes catalyze the covalent attachment of particular amino acids to the terminal adenosine of cognate tRNA substrates. In general, there is one synthetase for each of the twenty amino acids and each enzyme must discriminate against all of the cellular tRNAs that are specific for the nineteen noncognate amino acids. Primary sequence information combined with structural data have resulted in the division of the twenty synthetases into two classes. In recent years, several high-resolution co-crystal structures along with biochemical data have led to an increased understanding of tRNA recognition by synthetases of both classes. The anticodon sequence and the amino acid acceptor stem are the most common locations for critical recognition elements. This review will focus on acceptor stem discrimination by class II synthetases. In particular, the results of in vitro aminoacylation assays and site-directed and atomic group mutagenesis studies will be discussed. These studies have revealed that even subtle atomic determinants can provide signals for specific tRNA aminoacylation.

• 한국동물학회지
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• 제35권2호
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• pp.203-210
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• 1992

Hsp70, a 70 kDa protein, is the maior protein expressed when cells are heat-shocked. A cDNA library from mouse ID13 cells was screened with the human hsp70 gene as a probe, and a positive clone was obtained. The positive clone was subcloned into puc19 and the precise restriction was obtained. The CDNA was sequenced by the Sanger's dideoxv termination method. Single open reading frame that codes for a protein of 70 kDa was found. The DNA sequence of the cloned mouse DNA shows great homology (66-90%) with other mouse hsp70 genes and somewhat less homology (50",) with E. coli hsp70 gene (dnak). With the exception of one amino acid, the protein sequence deduced from the CDNA is identical to the mouse that shock cognate protein 70 (hsc70) that is constitutivelv expressed at normal temperature. The result suggests that the cloned CDNA encodes a hsc70 family rather than a heatinducible family.mily.

• Journal of Information Processing Systems
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• 제8권2호
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• pp.301-314
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• 2012

In this paper, two new approaches to align English-Arabic sentences in bilingual parallel corpora based on the Multi-Class Support Vector Machine (MSVM) and the Hidden Markov Model (HMM) classifiers are presented. A feature vector is extracted from the text pair that is under consideration. This vector contains text features such as length, punctuation score, and cognate score values. A set of manually prepared training data was assigned to train the Multi-Class Support Vector Machine and Hidden Markov Model. Another set of data was used for testing. The results of the MSVM and HMM outperform the results of the length based approach. Moreover these new approaches are valid for any language pairs and are quite flexible since the feature vector may contain less, more, or different features, such as a lexical matching feature and Hanzi characters in Japanese-Chinese texts, than the ones used in the current research.

• Environmental Analysis Health and Toxicology
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• 제22권3호
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• pp.197-202
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• 2007

구리는 환경에 광범위하게 존재하며, 생물체에게 필수적인 무기질이지만 고농도로 존재할 경우 독성을 발휘한다. 본 연구는 프로티옴 기술을 응용하여 수서태계에 구리와 같은 중금속의 존재 여부를 신속하게 평가하기 위한 생물지표를 발굴하기 위하여 수행되었다. 즉, 송사리(Oryzias latipes)를 이용하여 여러 농도의 구리용액(0.1, 1, 5 mg/L)에 24시간 노출시킨 다음, 머리부분에서 선택적으로 발현이 증가되는 단백질을 동정하고자 시도하였다. 본 시스템에서 유의적으로 발현이 증가하는 것으로 나타난 단백질은 beta-tubulin, heat shock cognate 70 (hsc70)이었으며, 이 결과의 일부를 semi-quantitative RT-PCR를 이용하여 확인하였다. 이와 같이 구리 처리에 특이적으로 발현이 증가된 송사리 단백질들은 노출평가를 위한 생물지표로서 개발을 위하여 더 연구할 가치가 있는 것으로 평가된다.

• Molecules and Cells
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• 제37권3호
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• pp.196-201
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• 2014

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by the vascular remodeling of the pulmonary arterioles, including formation of plexiform and concentric lesions comprised of proliferative vascular cells. Clinically, PAH leads to increased pulmonary arterial pressure and subsequent right ventricular failure. Existing therapies have improved the outcome but mortality still remains exceedingly high. There is emerging evidence that the seven-transmembrane G-protein coupled receptor APJ and its cognate endogenous ligand apelin are important in the maintenance of pulmonary vascular homeostasis through the targeting of critical mediators, such as Kr$\ddot{u}$ppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and microRNAs (miRNAs). Disruption of this pathway plays a major part in the pathogenesis of PAH. Given its role in the maintenance of pulmonary vascular homeostasis, the apelin-APJ pathway is a potential target for PAH therapy. This review highlights the current state in the understanding of the apelin-APJ axis related to PAH and discusses the therapeutic potential of this signaling pathway as a novel paradigm of PAH therapy.

• Journal of Microbiology and Biotechnology
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• 제29권6호
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• pp.897-904
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• 2019

Monascus purpureus recombinant mppC and mpp7 knockout strains were subjected to extractive fermentation in the context of azaphilone pigment production. Inclusion of Diaion HP-20 resin resulted in the selective production of unreduced azaphilone congeners, in addition to the early intermediate FK17-P2a, from ${\Delta}mppC$ and ${\Delta}mpp7$ strains that would otherwise mainly produce reduced congeners. Structural determination of two novel unreduced azaphilones from the ${\Delta}mpp7$ strain was accomplished. The unreduced azaphilone compound was converted into the cognate reduced congener in recombinant M. purpureus strains, demonstrating its intermediate role in azaphilone biosynthesis. This study demonstrates the possibility that extractive fermentation with Diaion HP-20 resin can be used to obtain cryptic azaphilone metabolites.

• BMB Reports
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• 제53권12호
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• pp.611-621
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• 2020

Bacterial endoribonuclease toxins belong to a protein family that inhibits bacterial growth by degrading mRNA or rRNA sequences. The toxin genes are organized in pairs with its cognate antitoxins in the chromosome and thus the activities of the toxins are antagonized by antitoxin proteins or RNAs during active translation. In response to a variety of cellular stresses, the endoribonuclease toxins appear to be released from antitoxin molecules via proteolytic cleavage of antitoxin proteins or preferential degradation of antitoxin RNAs and cleave a diverse range of mRNA or rRNA sequences in a sequence-specific or codon-specific manner, resulting in various biological phenomena such as antibiotic tolerance and persister cell formation. Given that substrate specificity of each endoribonuclease toxin is determined by its structure and the composition of active site residues, we summarize the biology, structure, and substrate specificity of the updated bacterial endoribonuclease toxins.

• IMMUNE NETWORK
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• 제16권2호
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• pp.134-139
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• 2016

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.