• Title/Summary/Keyword: protein structures

Search Result 593, Processing Time 0.031 seconds

Binding Models of Flavonols to Human Vascular Endothelial Growth Factor Receptor 2

  • Lee, Jee-Young;Jeong, Ki-Woong;Kim, Woong-Hee;Heo, Yong-Seok;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
    • /
    • v.30 no.9
    • /
    • pp.2083-2086
    • /
    • 2009
  • Human vascular endothelial growth factor receptor 2 (hVEGFR2) is an important signaling protein involved in angiogenesis and attractive drug target in cancer therapy. It has been reported that flavonols, a class of flavonoids, have anti-angiogenic activity in various cancer cell lines. We performed receptor-oriented pharmacophore based in silico screening for identification of hVEGFR2 inhibitors from flavonol database. By comparing with three X-ray complex structures of hVEGFR2 and its inhibitors, we evaluated the specific interactions between inhibitors and receptors and determined a single pharmacophore map. This map consisted of four features, a hydrogen bonding acceptor (HBA) on Cys917, two hydrogen bonding donors on Glu917 (HBD1) and Glu883 (HBD2), and one hydrophobic interaction (Lipo) with Val846, Ala864, Val897, Val914 and Phe1045 of hVEGFR2. Using this map, we searched a flavonol database including 9 typical flavonols and proposed that five flavonols, kaempferol, quercetin, fisetin, morin, and rhamnetin can be potent inhibitors of hVEGFR2. 3-OH of C-ring and 4’-OH of B-ring of flavonols are the essential features for hVEGFR2 inhibition. This study will be helpful for understanding the mechanism of inhibition of hVEGFR2 by natural products.

Cell Structures of Spermatogenesis of Rainbow Trout, Oncorhynchus mykiss in Reproductive Cycles (번식주기(繁殖週期)에 따른 무지개 송어(松魚) 정자형성시(精子形成時) 세포구조(細胞構造)의 변화(變化))

  • Yoon, Jong-Man;Kim, Gye-Woong;Park, Chung-Kil;Roh, Soon-Chang
    • Applied Microscopy
    • /
    • v.24 no.3
    • /
    • pp.55-66
    • /
    • 1994
  • This study was carried out to investigate the histological changes of sperm cells in testis, obtained from 100 of 3-year-old male rainbow trout (Oncorhynchus mykiss) collected and analysed from March in 1992 to February in 1993. Especially, the ultrastructural changes of spermatogonia, primary and secondary spermatocytes, spermatids, and spermatozoa were examined to describe the reproductive cycles of this species. The results obtained in this study were as follows: The ultrastructures of the gonadotrophs largely parallel the cyclical changes in the testes. Each nest of cells belongs to one spermatogenetic stage, although nests at different stages can be found within the one lobule. At first keterochromatin is dispersed and then is condensed. In mature gamete, the nucleus is dense and homogeneous. The nuclear membrane appeared at the beginning of differentiation. In spermatogonia, Sertoli cells are located at the periphery of their cytoplasm. In the primary spermatocytes, the small mitochondria are abundant over the outer cytoplasm. During cell differentiation, the cytoplasm decreases and the nucleus increases. In spermatids, the protein masses moved towards the posterior part of the nucleus. In late spermatids, the two large mitochondria are located over the cytoplasm. In spermatozoa, two spheroidal mitochondria (about 145nm long) are situated in parallel between the nucleus and the axoneme. Spermatozoa mitochondria are assembled into an organized sheath surrounding the outer dense fibres and axoneme of the flagellar midpiece. The two centrioles are quite separate and the central pair and sheath complex of the flagellum is inserted into the base of the distal centriole.

  • PDF

The Pharmacology of Botulinum Toxin (보툴리눔 독소의 약리)

  • Lee, Sang Hyuk;Lee, Hyun Sub;Jin, Sung Min
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
    • /
    • v.23 no.2
    • /
    • pp.93-98
    • /
    • 2012
  • Botulinum toxins are the most potent toxins known to mankind. Botulinum toxin acts by blocking the cholinergic neuromuscular or the cholinergic autonomic innervation of exocrine glands and smooth muscles. Seven distinct antigenic botulinum toxins (A, B, C, D, E, F and G) produced by different strains of Clostridium botulinum have been described and only A and B type of botulinum toxins were clinically used. Toxins were consisted of a heavy chain with a molecular weight of 100 kD and a light chain with a molecular weight of 50 kD. Toxins are bound with an astounding selectivity to glycoprotein structures located on the cholinergic nerve terminal. Subsequently light chain of toxin is internalized and cleaves different proteins of the acetylcholine transport protein cascade transporting the acetylcholine vesicle from the intracellular space into the synaptic cleft. After a decade of therapeutic application of the toxin, no anaphylaxis or deaths have been reported and systemic adverse effects have not been reported so far. However the toxin's immunologic properties can lead to the stimulation of antibody production, potentially rendering further treatments ineffective. Botulinum toxin is a safe and effective treatment. Use of botulinum toxin in clinical medicine has grown exponentially in recent years, and many parts of the human body are now being targeted for therapeutic purposes.

  • PDF

Alu sequences and molecular features (Alu 서열과 분자생물학적 특징)

  • Park Eun-Sil;Hong Kyung-Won;Kim Heui-Soo
    • Journal of Life Science
    • /
    • v.14 no.6 s.67
    • /
    • pp.1028-1039
    • /
    • 2004
  • During the past 65 million years, Alu sequences have been amplified through RNA-polymerase IIIderived transcripts, and have reached the copy number of about 1.4 million in primate genomes. They are the largest family among mobile genetic elements in human genome and consist of ten percent of the human genome. Alu sequences are thought to be functionless genetically, but many researchers have proved new function and disease implication. Alu elements make the genome insertional mutation, Alu-mediated recombination events, and unexpected splicing site and change gene structures, protein sequences, splicing motifs and expression patterns. In this review, the structure and origin of Alu, consensus sequences of Alu subfamilies, evolution and distribution of Alu, and their related diseases were described. We also indicated new research direction of Alu elements in relation to evolution and disease.

A Study on Collecting and Structuring Language Resource for Named Entity Recognition and Relation Extraction from Biomedical Abstracts (생의학 분야 학술 논문에서의 개체명 인식 및 관계 추출을 위한 언어 자원 수집 및 통합적 구조화 방안 연구)

  • Kang, Seul-Ki;Choi, Yun-Soo;Choi, Sung-Pil
    • Journal of the Korean Society for Library and Information Science
    • /
    • v.51 no.4
    • /
    • pp.227-248
    • /
    • 2017
  • This paper introduces an integrated model for systematically constructing a linguistic resource database that can be used by machine learning-based biomedical information extraction systems. The proposed method suggests an orderly process of collecting and constructing dictionaries and training sets for both named-entity recognition and relation extraction. Multiple heterogeneous structures for the resources which are collected from diverse sources are analyzed to derive essential items and fields for constructing the integrated database. All the collected resources are converted and refined to build an integrated linguistic resource storage. In this paper, we constructed entity dictionaries of gene, protein, disease and drug, which are considered core linguistic elements or core named entities in the biomedical domains and conducted verification tests to measure their acceptability.

Structural Basis for Recognition of L-lysine, L-ornithine, and L-2,4-diamino Butyric Acid by Lysine Cyclodeaminase

  • Min, Kyungjin;Yoon, Hye-Jin;Matsuura, Atsushi;Kim, Yong Hwan;Lee, Hyung Ho
    • Molecules and Cells
    • /
    • v.41 no.4
    • /
    • pp.331-341
    • /
    • 2018
  • L-pipecolic acid is a non-protein amino acid commonly found in plants, animals, and microorganisms. It is a well-known precursor to numerous microbial secondary metabolites and pharmaceuticals, including anticancer agents, immunosuppressants, and several antibiotics. Lysine cyclodeaminase (LCD) catalyzes ${\beta}$-deamination of L-lysine into L-pipecolic acid using ${\beta}$-nicotinamide adenine dinucleotide as a cofactor. Expression of a human homolog of LCD, ${\mu}$-crystallin, is elevated in prostate cancer patients. To understand the structural features and catalytic mechanisms of LCD, we determined the crystal structures of Streptomyces pristinaespiralis LCD (SpLCD) in (i) a binary complex with $NAD^+$, (ii) a ternary complex with $NAD^+$ and L-pipecolic acid, (iii) a ternary complex with $NAD^+$ and L-proline, and (iv) a ternary complex with $NAD^+$ and L-2,4-diamino butyric acid. The overall structure of SpLCD was similar to that of ornithine cyclodeaminase from Pseudomonas putida. In addition, SpLCD recognized L-lysine, L-ornithine, and L-2,4-diamino butyric acid despite differences in the active site, including differences in hydrogen bonding by Asp236, which corresponds with Asp228 from Pseudomonas putida ornithine cyclodeaminase. The substrate binding pocket of SpLCD allowed substrates smaller than lysine to bind, thus enabling binding to ornithine and L-2,4-diamino butyric acid. Our structural and biochemical data facilitate a detailed understanding of substrate and product recognition, thus providing evidence for a reaction mechanism for SpLCD. The proposed mechanism is unusual in that $NAD^+$ is initially converted into NADH and then reverted back into $NAD^+$ at a late stage of the reaction.

Probing Starch Biosynthesis Enzyme Isoforms by Visualization of Conserved Secondary Structure Patterns

  • Vorapreeda, Tayvich;Kittichotirat, Weerayuth;Meechai, Asawin;Bhumiratana, Sakarindr;Cheevadhanarak, Supapon
    • Proceedings of the Korean Society for Bioinformatics Conference
    • /
    • 2005.09a
    • /
    • pp.215-220
    • /
    • 2005
  • Generally, enzymes in the starch biosynthesis pathway exist in many isoforms, contributing to the difficulties in the dissection of their specific roles in controlling starch properties. In this study, we present an algorithm as an alternative method to classify isoforms of starch biosynthesis enzymes based on their conserved secondary structures. Analysis of the predicted secondary structure of plant soluble starch synthase I (SSI) and soluble starch synthase II (SSII) demonstrates that these two classes of isoform can be reclassified into three subsets, SS-A, SS-B and SS-C, according to the differences in the secondary structure of the protein at C-terminus. SS-A reveals unique structural features that are conserved only in cereal plants, while those of SS-B are found in all plants and SS-C is restricted to barley. These findings enable us to increase the accuracy in the estimation of evolutionary distance between isoforms of starch synthases. Moreover, it facilitates the elucidation of correlations between the functions of each enzyme isoforms and the properties of starches. Our secondary structure analysis tool can be applicable to study the functions of other plant enzyme isoforms of economical importance.

  • PDF

Usage of Tobacco Plants for Various Purposes (담배 속 식물의 다양한 활용방안 모색)

  • Um, Yu-Rry;Lee, Moon-Soon;Lee, Yi;Seok, Yeong-Seon
    • Journal of the Korean Society of Tobacco Science
    • /
    • v.33 no.1
    • /
    • pp.8-15
    • /
    • 2011
  • Genus Nicotiana has 76 species including N. tabacum. These plants are used not only as a material for cigarette manufacturing but also as ornamental plant, medicinal plant, poisonous substance plant, and bug repellent plant. N. tabacum is used as a main material for cigarette manufacturing with N. rustica. N. sylvestris and N. alata is used as ornamental plants because of their beautiful flowers and N. rustica is used for bug repellent or pesticide because of its high concentration of nicotine. N. glauca, a tree tobacco, is used for bio-fuel production. N. tabacum is used as a popular model plant system for degeneration, regeneration, and transformation. N. benthamiana is also used as a model system for foreign gene expression by agroinfiltration. The transformation ability of tobacco plant is a good target for molecular farming. Hepatitis B virus envelop protein, E. coli heat-labile enterotoxin, diabetes autoantigen, and cholera toxin B subunit were produced using tobacco plants. Secondary metabolites of tobacco include nicotine, anabasine, nornicotine, anatabine, cembranoid, solanesol, linoleic acid, rutin, lignin and sistosterol, and they are used for various medicine productions which cannot be produced by organic synthesis for their complicated structures. In conclusion, we have to understand the applicability of tobacco plant in detail and study to enlarge the usage of the plants.

Effects of Sayeok-tang on Papain-Induced Osteoarthritis in Mice (Papain으로 유도된 골관절염 생쥐 모델에서 사역탕(四逆湯)의 항골관절염 효능에 관한 연구)

  • Kung, Shyang En;Oh, Min Seok
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.27 no.2
    • /
    • pp.212-224
    • /
    • 2013
  • This study intends to clarify how Sayeok-tang(here in after reffered to SYT) affect C57BL/10 mice whose osteoarthritis was induced by papain. Osteoarthritis was induced by injecting papain in the knee joint of 3 groups(n=6) of mice. Normal group was non-treatment group and was not injected papain, whereas control mice were orally administered with $200{\mu}{\ell}$ of physiological saline. Positive comparison group was medicated with 100 mg/kg of Joins$^{(R)}$ mixed with $200{\mu}{\ell}$ of physiological saline. Experimental group was medicated with 400 mg/kg of SYT mixed with $200{\mu}{\ell}$ of physiological saline. Both Positive and experimental comparison groups were orally medicated once per day for 4 weeks. After the experiment, the functions of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological changes in the knee joint structures were observed. As results, SYT had no significant effect on the liver and kidney functions. Interleukin-$1{\beta}$(IL-$1{\beta}$), interleukin-6(IL-6), monocyte chemo attractant protein-1(MCP-1) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were significantly decreased. Inflammation cytokines in joints were all significantly decreased. Prostaglandin $E_2(PGE_2)$, thromboxane $B_2(TXB_2)$ were significantly decreased. Destruction of cartilage on micro computed tomography(CT)-arthrography was meaningfully decreased. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small. Based on all results mentioned above, Sayeok-tang(SYT) is believed to be meaningful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

Sequence Analysis, Molecular Cloning and Restriction Mapping of Mitochondreal Genome of Domesticated Silkworm, Bombyx mori (누에 미토콘드리아 유전체의 제한효소 지도작성, 클로닝 및 염기서열 분석)

  • 이진성;성승현;김용성;서동상
    • Journal of Sericultural and Entomological Science
    • /
    • v.42 no.1
    • /
    • pp.14-23
    • /
    • 2000
  • The mitochondrial genome of domesticated silkworm (Bombyx mori) was mapped with five restriction endonucleases (BamHI, EcoRI, HindIII, PstI and XbaI), the entire genome was cloned with HindIII and EcoRI. From the end sequencing results of 5$^1$and 3$^1$region for full genome set of eleven mitochondrial clones, the seven mitochondrial genes (NADH dehydrogenase 6, ATPase 6, ATPase 8, tRN $A^{Lys}$, tRN $A^{Asp}$, tRN $A^{Thr}$ and tRN $A^{Phe}$ of mori were identified on the basis of their nucleotide sequence homology. The nucleotide composition of NADH dehydrogenase 6 was heavily biased towards adenine and thymine, which accounted for 87.76%. On basis of the sequence similarity with published tRNA genes from six insect species, the tRN $A^{Lys}$, tRN $A^{Asp}$ and tRN $A^{Thr}$ were showed stable canonical clover-leaf tRNA structures with acceptible anticodons. However, both the DHU and T$\psi$C arms of tRN $A^{Phe}$ could not form any stable stem-loop structure. The two overlapping gene pairs (tRN $A^{Lys}$ -tRN $A^{ASP}$ and ATPase8-ATPase6) were found from our sequencing results. The genes are encoded on the same strad. ATPase8 and ATPase6 overlaps (ATGATAA) which are a single example of overlapping events between abutted protein-coding genes are common, and there is evidence that the two proteins are transcribed from a single bicistronic message by initiation at 5$^1$terminal start site for ATPase8 and at an internal start site for ATPase6. Ultimately, this result will provide assistance in designing oligo-nucleotides for PCR amplification, and sequencing the specific mitochondrial genes for phylogenetics of geographic races, genetically improved silkworm strains and wild silkworm (mandarina) which is estimated as ancestal of domesticated silkworm.sticated silkworm.

  • PDF