• 제목/요약/키워드: protein function evidence

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Classifying Biomedical Literature Providing Protein Function Evidence

  • Lim, Joon-Ho;Lee, Kyu-Chul
    • ETRI Journal
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    • 제37권4호
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    • pp.813-823
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    • 2015
  • Because protein is a primary element responsible for biological or biochemical roles in living bodies, protein function is the core and basis information for biomedical studies. However, recent advances in bio technologies have created an explosive increase in the amount of published literature; therefore, biomedical researchers have a hard time finding needed protein function information. In this paper, a classification system for biomedical literature providing protein function evidence is proposed. Note that, despite our best efforts, we have been unable to find previous studies on the proposed issue. To classify papers based on protein function evidence, we should consider whether the main claim of a paper is to assert a protein function. We, therefore, propose two novel features - protein and assertion. Our experimental results show a classification performance with 71.89% precision, 90.0% recall, and a 79.94% F-measure. In addition, to verify the usefulness of the proposed classification system, two case study applications are investigated - information retrieval for protein function and automatic summarization for protein function text. It is shown that the proposed classification system can be successfully applied to these applications.

Directional adjacency-score function for protein fold recognition

  • Heo, Mu-Young;Cheon, Moo-Kyung;Kim, Suhk-Mann;Chung, Kwang-Hoon;Chang, Ik-Soo
    • Interdisciplinary Bio Central
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    • 제1권2호
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    • pp.8.1-8.6
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    • 2009
  • Introduction: It is a challenge to design a protein score function which stabilizes the native structures of many proteins simultaneously. The coarse-grained description of proteins to construct the pairwise-contact score function usually ignores the backbone directionality of protein structures. We propose a new two-body score function which stabilizes all native states of 1,006 proteins simultaneously. This two-body score function differs from the usual pairwise-contact functions in that it considers two adjacent amino acids at two ends of each peptide bond with the backbone directionality from the N-terminal to the C-terminal. The score is a corresponding propensity for a directional alignment of two adjacent amino acids with their local environments. Results and Discussion: We show that the construction of a directional adjacency-score function was achieved using 1,006 training proteins with the sequence homology less than 30%, which include all representatives of different protein classes. After parameterizing the local environments of amino acids into 9 categories depending on three secondary structures and three kinds of hydrophobicity of amino acids, the 32,400 adjacency-scores of amino acids could be determined by the perceptron learning and the protein threading. These could stabilize simultaneously all native folds of 1,006 training proteins. When these parameters are tested on the new distinct 382 proteins with the sequence homology less than 90%, 371 (97.1%) proteins could recognize their native folds. We also showed using these parameters that the retro sequence of the SH3 domain, the B domain of Staphylococcal protein A, and the B1 domain of Streptococcal protein G could not be stabilized to fold, which agrees with the experimental evidence.

Expression in Escherichia coli of a Putative Human Acetohydroxyacid Synthase

  • Duggleby, Ronald G.;Kartikasari, Apriliana E.R.;Wunsch, Rebecca M.;Lee, Yu-Ting;Kil, Mee-Wha;Shin, Ju-Young;Chang, Soo-Ik
    • BMB Reports
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    • 제33권3호
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    • pp.195-201
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    • 2000
  • A human gene has been reported that may encode the enzyme acetohydroxyacid synthase. Previously this enzyme was thought to be absent from animals although it is present in plants and many microorganisms. In plants, this enzyme is the target of a number of commercial herbicides and the use of these compounds may need to be reassessed if the human enzyme exists and proves to be susceptible to inhibition. Here we report the construction of several plasmid vectors containing the cDNA sequence for this protein, and their expression in Escherichia coli. High levels of expression were observed, but most of the protein proved to be insoluble. The small amounts of soluble protein contained little or no acetohydroxyacid synthase activity. Attempts to refold the insoluble protein were successful insofar as the protein became soluble. However, the refolded protein did not gain any acetohydroxyacid synthase activity. In vivo complementation tests of an E. coli mutant produced no evidence that the protein is active. Incorrect folding, or the lack of another subunit, may explain the data but we favor the interpretation that this gene does not encode an acetohydroxyacid synthase.

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Transforming Stimulated Clone 22 (TSC-22) Interacts Directly with Bromodomain-Containing Protein 7 (BRD7) to Enhance the Inhibition of Extracellular Signal-Regulate Kinase (ERK) Pathway in Ovarian Cancer

  • Lee, Seung-Hoon;Choi, Donchan
    • 한국발생생물학회지:발생과생식
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    • 제26권3호
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    • pp.117-126
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    • 2022
  • Bromodomain-containing protein 7 (BRD7) participates in many cellular processes and embryo development. BRD7 is down-regulated in various cancers and evidence of its tumor suppressor function has been accumulating. Here, we identified transforming stimulated clone 22 (TSC-22) as a novel BRD7 interacting protein and show its novel function as a positive regulator of BRD7. We found that TSC-22 expression potentiated the inactivation of the extracellular signal-regulate kinase (ERK) pathway by BRD7. Our data establishes TSC-22 as a modulator of BRD7 and unravels the molecular mechanisms that drive the synergistic tumor-suppressing effects of TSC-22 and BRD7. Our findings may open new avenues for developing novel molecular therapies for tumors exhibiting down-regulated BRD7 and/or TSC-22.

Understanding Enzyme Structure and Function in Terms of the Shifting Specificity Model

  • Britt, Billy Mark
    • BMB Reports
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    • 제37권4호
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    • pp.394-401
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    • 2004
  • The purpose of this paper is to suggest that the prominence of Haldane's explanation for enzyme catalysis significantly hinders investigations in understanding enzyme structure and function. This occurs despite the existence of much evidence that the Haldane model cannot embrace. Some of the evidence, in fact, disproves the model. A brief history of the explanation of enzyme catalysis is presented. The currently accepted view of enzyme catalysis -- the Haldane model -- is examined in terms of its strengths and weaknesses. An alternate model for general enzyme catalysis (the Shifting Specificity model) is reintroduced and an assessment of why it may be superior to the Haldane model is presented. Finally, it is proposed that a re-examination of many current aspects in enzyme structure and function (specifically, protein folding, x-ray and NMR structure analyses, enzyme stability curves, enzyme mimics, catalytic antibodies, and the loose packing of enzyme folded forms) in terms of the new model may offer crucial insights.

Pathophysiological Role of S-Nitrosylation and Transnitrosylation Depending on S-Nitrosoglutathione Levels Regulated by S-Nitrosoglutathione Reductase

  • Choi, Min Sik
    • Biomolecules & Therapeutics
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    • 제26권6호
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    • pp.533-538
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    • 2018
  • Nitric oxide (NO) mediates various physiological and pathological processes, including cell proliferation, differentiation, and inflammation. Protein S-nitrosylation (SNO), a NO-mediated reversible protein modification, leads to changes in the activity and function of target proteins. Recent findings on protein-protein transnitrosylation reactions (transfer of an NO group from one protein to another) have unveiled the mechanism of NO modulation of specific signaling pathways. The intracellular level of S-nitrosoglutathione (GSNO), a major reactive NO species, is controlled by GSNO reductase (GSNOR), a major regulator of NO/SNO signaling. Increasing number of GSNOR-related studies have shown the important role that denitrosylation plays in cellular NO/SNO homeostasis and human pathophysiology. This review introduces recent evidence of GSNO-mediated NO/SNO signaling depending on GSNOR expression or activity. In addition, the applicability of GSNOR as a target for drug therapy will be discussed in this review.

Combining the Power of Advanced Proteome-wide Sample Preparation Methods and Mass Spectrometry for defining the RNA-Protein Interactions

  • Liu, Tong;Xia, Chaoshuang;Li, Xianyu;Yang, Hongjun
    • Mass Spectrometry Letters
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    • 제13권4호
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    • pp.115-124
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    • 2022
  • Emerging evidence has shown that RNA-binding proteins (RBPs) dynamically regulate all aspects of RNA in cells and involve in major biological processes of RNA, including splicing, modification, transport, transcription and degradation. RBPs, as powerful and versatile regulatory molecule, are essential to maintain cellular homeostasis. Perturbation of RNA-protein interactions and aberration of RBPs function is associated with diverse diseases, such as cancer, autoimmune disease, and neurological disorders. Therefore, it is crucial to systematically investigate the RNA-binding proteome for understanding interactions of RNA with proteins. Thanks to the development of the mass spectrometry, a variety of proteome-wide methods have been explored to define comprehensively RNA-protein interactions in recent years and thereby contributed to speeding up the study of RNA biology. In this review, we systematically described these methods and summarized the advantages and disadvantages of each method.

정상 성인의 신체조성과 폐 기능의 연관성 (Correlation between Body Composition and Lung Function in Healthy Adults)

  • 김현승;조성현
    • 대한통합의학회지
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    • 제8권2호
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    • pp.53-61
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    • 2020
  • Purpose : We investigated the correlation between body composition and lung function in healthy adults. Methods : This study included 204 healthy adults in whom all measurements were obtained once, and all data were analyzed using the SPSS software for Windows, version 22.0. Pearson's correlation analysis was performed to determine the correlation between body composition (represented by the total body water, protein mass, soft lean mass, mineral mass, basal metabolic rate, fat-free mass, skeletal muscle mass, and body fat percentage) and lung function (represented by the forced vital capacity [FVC], forced expiratory volume in 1 second [FEV1], the FEV1/FVC ratio, maximum voluntary ventilation [MVV], maximum expiratory pressure [MEP], and the maximum inspiratory pressure [MIP]). All measurements were obtained by two investigators to improve reliability. A significance level of α=.05 was used to verify statistical significance. Results : Among the lung function measurements obtained in both men and women, the FVC, FEV1, MVV, and MIP were positively correlated with the total body water, protein mass, soft lean mass, mineral mass, basal metabolic rate, fat-free mass, and skeletal muscle mass in men (p<.05). The FEV1/FVC ratio was negatively correlated with the total body water, soft lean mass, mineral mass, basal metabolic rate, fat-free mass and the body fat percentage (p<.05). Notably, the FVC, FEV1, and MVV were positively correlated with the total body water, protein mass, soft lean mass, mineral mass, basal metabolic rate, fat-free mass, and skeletal muscle mass in women (p<.05). Conclusion : This study showed a significant correlation between body composition and lung function in healthy adults. In combination with future studies on lung function, our results can provide objective evidence regarding the importance of prevention of lung disease, and our data can be utilized in rehabilitation programs for patients with respiratory diseases.

SCYL1BP1 has Tumor-suppressive Functions in Human Lung Squamous Carcinoma Cells by Regulating Degradation of MDM2

  • Yang, Zhi-Ping;Xie, Yong-Hong;Ling, Dan-Yan;Li, Jin-Rui;Jiang, Jin;Fan, Yao-Hua;Zheng, Jia-Lian;Wu, Wan-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권17호
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    • pp.7467-7471
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    • 2014
  • SCY1-like 1-binding protein 1 (SCYL1BP1) is a newly identified transcriptional activator domain containing protein with many unknown biological functions. Recently emerging evidence has revealed that it is a novel regulator of the p53 pathway, which is very important for the development of human cancer. However, the effects of SCYL1BP1 on human lung squamous carcinoma cell biological behavior remain poorly understood. In this study, we present evidence that SCYL1BP1 can promote the degradation of MDM2 protein and further inhibit the G1/S transition of lung squamous carcinoma cell lines. Functional assays found that reintroduction of SCYL1BP1 into lung squamous carcinoma cell lines significantly inhibited cell proliferation, migration, invasion and tumor formation in nude mice, suggesting strong tumor suppressive function of SCYL1BP1 in lung squamous carcinoma. Taken together, our data suggest that the interaction of SCYL1BP1/MDM2 could accelerate MDM2 degradation, and may function as an important tumor suppressor in lung squamous carcinomas.

Structural insights showing how arginine is able to be glycosylated by pathogenic effector proteins

  • Park, Jun Bae;Yoo, Youngki;Cho, Hyun-Soo
    • BMB Reports
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    • 제51권12호
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    • pp.609-610
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    • 2018
  • Glycosylation is one form of protein modification and plays a key role in protein stability, function, signaling regulation and even cancer. NleB and SseK are bacterial effector proteins and possess glycosyltransferase activity, even though they have different substrate preferences. NleB/SseKs transfer the GlcNAc sugar to an arginine residue of host proteins, leading to reduced $NF-{\kappa}B-dependent$ responses. By combining X-ray crystallography, NMR, molecular dynamics, enzyme kinetic assays and in vivo experiments, we demonstrated that a conserved HEN (His-Glu-Asn) motif in the active site plays a key role in enzyme catalysis and virulence. The lid-domain regulates the opening and closing of the active site and the HLH domain determines the substrate specificity. Our findings provide evidence for the enzymatic mechanism by which arginine can be glycosylated by SseK/NleB enzymes.