• Title/Summary/Keyword: Structural Modification

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Computational Analysis of the 3-D structure of Human GPR87 Protein: Implications for Structure-Based Drug Design

  • Rani, Mukta;Nischal, Anuradha;Sahoo, Ganesh Chandra;Khattri, Sanjay
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7473-7482
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    • 2013
  • The G-protein coupled receptor 87 (GPR87) is a recently discovered orphan GPCR which means that the search of their endogenous ligands has been a novel challenge. GPR87 has been shown to be overexpressed in squamous cell carcinomas (SCCs) or adenocarcinomas in lungs and bladder. The 3D structure of GPR87 was here modeled using two templates (2VT4 and 2ZIY) by a threading method. Functional assignment of GPR87 by SVM revealed that along with transporter activity, various novel functions were predicted. The 3D structure was further validated by comparison with structural features of the templates through Verify-3D, ProSA and ERRAT for determining correct stereochemical parameters. The resulting model was evaluated by Ramachandran plot and good 3D structure compatibility was evidenced by DOPE score. Molecular dynamics simulation and solvation of protein were studied through explicit spherical boundaries with a harmonic restraint membrane water system. A DRY-motif (Asp-Arg-Tyr sequence) was found at the end of transmembrane helix3, where GPCR binds and thus activation of signals is transduced. In a search for better inhibitors of GPR87, in silico modification of some substrate ligands was carried out to form polar interactions with Arg115 and Lys296. Thus, this study provides early insights into the structure of a major drug target for SCCs.

A Novel Strategy for Thermostability Improvement of Trypsin Based on N-Glycosylation within the Ω-Loop Region

  • Guo, Chao;Liu, Ye;Yu, Haoran;Du, Kun;Gan, Yiru;Huang, He
    • Journal of Microbiology and Biotechnology
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    • v.26 no.7
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    • pp.1163-1172
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    • 2016
  • The Ω-loop is a nonregular and flexible structure that plays an important role in molecular recognition, protein folding, and thermostability. In the present study, molecular dynamics simulation was carried out to assess the molecular stability and flexibility profile of the porcine trypsin structures. Two Ω-Loops (fragment 57-67 and fragment 78-91) were confirmed to represent the flexible region. Subsequently, glycosylation site-directed mutations (A73S, N84S, and R104S) were introduced within the Ω-loop region and its wing chain based on its potential N-glycosylation sites (Asn-Xaa-Ser/Thr consensus sequences) and structure information to improve the thermostability of trypsin. The result demonstrated that the half-life of the N84S mutant at 50℃ increased by 177.89 min when compared with that of the wild-type enzyme. Furthermore, the significant increase in the thermal stability of the N84S mutant has also been proven by an increase in the Tm values determined by circular dichroism. Additionally, the optimum temperatures of the wild-type enzyme and the N84S mutant were 75℃ and 80℃, respectively. In conclusion, we obtained the thermostability-improved enzyme N84S mutant, and the strategy used to design this mutant based on its structural information and N-linked glycosylation modification could be applied to engineer other enzymes to meet the needs of the biotechnological industry.

Chemical Modification of Botryosphaeran: Structural Characterization and Anticoagulant Activity of a Water-Soluble Sulfonated ($1{\rightarrow}3$)($1{\rightarrow}6$)-${\beta}$-D-Glucan

  • Brandi, Jamile;Oliveira, Eder C.;Monteiro, Nilson K.;Vasconcelos, Ana Flora D.;Dekker, Robert F.H.;Barbosa, Aneli M.;Silveira, Joana L.M.;Mourao, Paulo A.S.;Silva, Maria De Lourdes Corradi Da
    • Journal of Microbiology and Biotechnology
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    • v.21 no.10
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    • pp.1036-1042
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    • 2011
  • The exopolysaccharide botryosphaeran ($EPS_{GLC}$; a ($1{\rightarrow}3$)($1{\rightarrow}6$)-${\beta}$-D-glucan from Botryosphaeria rhodina MAMB-05) was sulfonated to produce a water-soluble fraction ($EPS_{GLC}$-S) using pyridine and chlorosulfonic acid in formamid. This procedure was then repeated twice to produce another fraction ($EPS_{GLC}$-RS) with a higher degree of substitution (DS, 1.64). The purity of each botryosphaeran sample (unsulfonated and sulfonated) was assessed by gel filtration chromatography (Sepharose CL-4B), where each polysaccharide was eluted as a single symmetrical peak. The structures of the sulfonated and re-sulfonated botryosphaerans were investigated using ultraviolet-visible (UV-Vis), Fourier-transform infrared (FT-IR), and $^{13}C$ nuclear magnetic resonance ($^{13}C$ NMR) spectroscopies. $EPS_{GLC}$ and $EPS_{GLC}$-RS were also assayed for anticoagulation activity, and $EPS_{GLC}$-RS was identified as an anticoagulant.

The effects of oxygen partial pressure on $SrTiO_3$ films with $RuO_2$ bottom electrode ($SrTiO_3/RuO_2$ 박막 형성시 플라즈마 가스 주입비의 영향)

  • 박치선;김상훈;마재평
    • Journal of the Korean Crystal Growth and Crystal Technology
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    • v.8 no.2
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    • pp.286-291
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    • 1998
  • $SrTiO_3$[ST] thin films were fabricated on $RuO_2$bottom electrodes by RF magnetron sputtering with various $Ar/O_2$ratio in sputtering gas. As the content of oxygen increases, the leakage current of ST films measured at $10^5$ V/cm decreases from $2.0{\times}10^{-6}A/{\textrm}{cm}^2(Ar/O_2=10/0)$ to $3.8{\times}10^{-7}A/{\textrm}cm^2(Ar/O_2=5/5)$, and the dielectric constant of ST films increases from $70(Ar/O_2=10/0)$ to $190(Ar/O_2=5/5)$. The improvement of electrical properties of ST films is mainly due to the structural modification of ST films such as better crystallinity, smooth surface morphology with the increase of oxygen content in the sputtering gas.

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Modification of Schottky Barrier Properties of Ti/p-type InP Schottky Diode by Polyaniline (PANI) Organic Interlayer

  • Reddy, P.R. Sekhar;Janardhanam, V.;Jyothi, I.;Yuk, Shim-Hoon;Reddy, V. Rajagopal;Jeong, Jae-Chan;Lee, Sung-Nam;Choi, Chel-Jong
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.16 no.5
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    • pp.664-674
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    • 2016
  • The electrical properties of Ti/p-type InP Schottky diodes with and without polyaniline (PANI) interlayer was investigated using current-voltage (I-V) and capacitance-voltage (C-V) measurements. The barrier height of Ti/p-type InP Schottky diode with PANI interlayer was higher than that of the conventional Ti/p-type InP Schottky diode, implying that the organic interlayer influenced the space-charge region of the Ti/p-type InP Schottky junction. At higher voltages, the current transport was dominated by the trap free space-charge-limited current and trap-filled space-charge-limited current in Ti/p-type InP Schottky diode without and with PANI interlayer, respectively. The domination of trap filled space-charge-limited current in Ti/p-type InP Schottky diode with PANI interlayer could be associated with the traps originated from structural defects prevailing in organic PANI interlayer.

Directed Evolution of Beta-galactosidase from Escherichia coli into Beta-glucuronidase

  • Xiong, Ai-Sheng;Peng, Ri-He;Zhuang, Jing;Liu, Jin-Ge;Xu, Fang;Cai, Bin;Guo, Zhao-Kui;Qiao, Yu-Shan;Chen, Jian-Min;Zhang, Zhen;Yao, Quan-Hong
    • BMB Reports
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    • v.40 no.3
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    • pp.419-425
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    • 2007
  • In vitro directed evolution through DNA shuffling is a powerful molecular tool for creation of new biological phenotypes. E. coli $\beta$-galactosidase and $\beta$-glucuronidase are widely used, and their biological function, catalytic mechanism, and molecular structures are well characterized. We applied an in vitro directed evolution strategy through DNA shuffling and obtained five mutants named YG6764, YG6768, YG6769, YG6770 and YG6771 after two rounds of DNA shuffling and screening, which exhibited more $\beta$-glucuronidase activity than wild-type $\beta$-galactosidase. These variants had mutations at fourteen nucleic acid sites, resulting in changes in ten amino acids: S193N, T266A, Q267R, V411A, D448G, G466A, L527I, M543I, Q626R and Q951R. We expressed and purified those mutant proteins. Compared to the wild-type protein, five mutant proteins exhibited high $\beta$-glucuronidase activity. The comparison of molecular models of the mutated and wildtype enzymes revealed the relationship between protein function and structural modification.

A Study on the Factors Affecting the Acceptance Intention for Mobile Ads. (모바일 광고의 수용의도에 영향을 미치는 요인에 관한 연구)

  • Yoo, Sang-Jin;Tang, Hung-Lian;Kim, Hyo-Jung
    • Information Systems Review
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    • v.9 no.1
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    • pp.1-21
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    • 2007
  • This research investigates the determinants of consumer's acceptance for the mobile Ads. Based on TAM(Technology Acceptance Model) and Flow theory, our research adopts some factors for a theoretical model such as entertainment, information, irritation, credibility, flow experience, attitudes and acceptance intention. For examining an implied relationships by this research model, a field study using survey methodology for data collection was conducted. This data was analyzed based on using AMOS, the structural equation modeling and a second generation multi variant technique, and has gained distinct advantages over other technique. After some model modification according to model generating strategy approach, this study shows that entertainment, irritation, credibility and flow experience have significant effects on the attitudes. And also, this attitudes have acceptance intention in mobile Ads. In conclusion, implications are discussed along with limitations and further research direction.

Pushover Analysis of a 5-Story RC OMRF Considering Inelastic Shear Behavior of Beam-Column Joint (보-기둥 접합부 비탄성 전단거동을 고려한 5층 철근콘크리트 보통모멘트골조의 푸쉬오버해석)

  • Kang, Suk-Bong;Kim, Tae-Yong
    • Journal of the Korea Concrete Institute
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    • v.24 no.5
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    • pp.517-524
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    • 2012
  • In this study, the effects of the inelastic shear behavior of beam-column joint and the vertical distribution of lateral load are evaluated considering higher modes on the response of RC OMRF using the pushover analysis. A structure used for the analysis was a 5-story structure located at site class SB and seismic design category C, which was designed in accordance with KBC2009. Bending moment-curvature relationship for beam and column was identified using fiber model. Also, bending moment-rotation relationship for beam-column joint was calculated using simple and unified joint shear behavior model and moment equilibrium relationship for the joint. The results of pushover analysis showed that, although the rigid beam-column joint overestimated the stiffness and strength of the structure, the inelastic shear behavior of beam-column joint could be neglected in the process of structural design since the average response modification factor satisfied the criteria of KBC2009 for RC OMRF independent to inelastic behavior of joint.

SnO2-Coated 3D Etched Cu Foam for Lithium-ion Battery Anode

  • Um, Ji Hyun;Kim, Hyunwoo;Cho, Yong-Hun;Yoon, Won-Sub
    • Journal of Electrochemical Science and Technology
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    • v.11 no.1
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    • pp.92-98
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    • 2020
  • SnO2-based high-capacity anode materials are attractive candidate for the next-generation high-performance lithium-ion batteries since the theoretical capacity of SnO2 can be ideally extended from 781 to 1494 mAh g-1. Here 3D etched Cu foam is applied as a current collector for electron path and simultaneously a substrate for the SnO2 coating, for developing an integrated electrode structure. We fabricate the 3D etched Cu foam through an auto-catalytic electroless plating method, and then coat the SnO2 onto the self-supporting substrate through a simple sol-gel method. The catalytic dissolution of Cu metal makes secondary pores of both several micrometers and several tens of micrometers at the surface of Cu foam strut, besides main channel-like interconnected pores. Especially, the additional surface pores on etched Cu foam are intended for penetrating the individual strut of Cu foam, and thereby increasing the surface area for SnO2 coating by using even the internal of Cu foam. The increased areal capacity with high structural integrity upon cycling is demonstrated in the SnO2-coated 3D etched Cu foam. This study not only prepares the etched Cu foam using the spontaneous chemical reactions but also demonstrates the potential for electroless plating method about surface modification on various metal substrates.

The Structural Path Model of Adolescents′ Internet Addiction and Expected Self-Control (청소년의 인터넷 중독현상과 자기통제기대의 구조적 경로모형에 관한 연구)

  • 박재성
    • Korean Journal of Health Education and Promotion
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    • v.21 no.3
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    • pp.1-17
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    • 2004
  • The purpose of this study is to evaluate the roles of expected self-control and expected self-control results in explaining adolescents' Internet addiction. In the study model, expectations of self-control and self-control results directly determine Internet addiction and Internet use time meditates the impacts of expectations of self-control and self-control results on Internet addiction. The study subjects are 1,080 middle and high school students in Busan. Stratified cluster sampling is applied by school type and school year. The response rate is 96%(l,037cases). This study develops the scales of expected self-control and expected self-control results. The scales of Internet addiction are devised by using the concept of functional dependency such as salience, withdrawal symptoms, mood modification, tolerance, relapse, and conflict. For verifying the study model, path analysis and multiple regression models are applied for identifying path significants and evaluating confounding effects of control variables, respectively. Moreover, multi partial F-test is performed for selecting the best regression model. Expected self-control is a significant determinant of Internet addiction and Internet use time that also significantly explains Internet addiction. The total effect of expected self-control towards Internet addiction is -.95. The total effect is comprised with the direct effect (-.71) and the indirect effect(-.24). In this result, the direct effect refers a curative effect since expected self-control directly reduces the level of Internet addiction, and the indirect effect refers a preventive effect because self-control can reduce time of Internet use that is a direct determinant of Internet addiction. In the test of the confounding effects of control variables, there are no confounding effects in the models of multiple regression. It implies a robustness of the study model as regards control variables. In conclusion, improving adolescents' expected self-control can control Internet addiction level. This finding implies that a health promotion program for improving expected self-control can be a cost effective method compared to other approaches.