• 제목/요약/키워드: PtpA

검색결과 178건 처리시간 0.026초

The Molecular Modeling of Novel Inhibitors of Protein Tyrosine Phosphatase 1B Based on Catechol by MD and MM-GB (PB)/SA Calculations

  • Kocakaya, Safak Ozhan
    • Bulletin of the Korean Chemical Society
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    • 제35권6호
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    • pp.1769-1776
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    • 2014
  • Binding modes of a series of catechol derivatives such as protein tyrosine phosphatase 1B (PTP1B) inhibitors were identified by molecular modeling techniques. Docking, molecular dynamics simulations and free energy calculations were employed to determine the modes of these new inhibitors. Binding free energies were calculated by involving different energy components using the Molecular Mechanics-Poisson-Boltzmann Surface Area and Generalized Born Surface Area methods. Relatively larger binding energies were obtained for the catechol derivatives compared to one of the PTP1B inhibitors already in use. The Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) free energy decomposition analysis indicated that the hydroxyl functional groups and biphenyl ring system had favorable interactions with Met258, Tyr46, Gln262 and Phe182 residues of PTP1B. The results of hydrogen bound analysis indicated that catechol derivatives, in addition to hydrogen bonding interactions, Val49, Ile219, Gln266, Asp181 and amino acid residues of PTP1B are responsible for governing the inhibitor potency of the compounds. The information generated from the present study should be useful for the design of more potent PTP1B inhibitors as anti-diabetic agents.

이더넷 네트워크의 시간 동기화 검증을 위한 IEEE 1588v2 PTP 구현 (Implementation of IEEE 1588v2 PTP for Time Synchronization Verification of Ethernet Network)

  • 김성진;고광만
    • 정보처리학회논문지A
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    • 제19A권4호
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    • pp.181-186
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    • 2012
  • 분산 환경의 계측 및 제어 시스템에서 분산된 디바이스들의 복잡한 동기화 구조를 해결하기 위한 기술의 필요성이 요구되며 그러한 분산시스템 환경에서 시간 동기화를 위해 IEEE 표준인 정밀 클럭 동기화 프로토콜(Precision Clock Synchronization Protocol)을 사용함으로써 문제를 해결 할 수 있다. 본 논문에서는 정확한 시간 동기화를 계측하기 위해 지연 요청-응답(Delay Request-Response) 메커니즘을 이용하여 IEEE 1588v2 PTP를 계측하고 제어 할 수 있는 기능을 BlueScope BL6000A에 구현하였다.

Anti-obesity and hypolipidemic effects of Rheum undulatum in high-fat diet-fed C57BL/6 mice through protein tyrosine phosphatase 1B inhibition

  • Lee, Woo-Jung;Yoon, Goo;Hwang, Ye-Ran;Kim, Yong-Kee;Kim, Su-Nam
    • BMB Reports
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    • 제45권3호
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    • pp.141-146
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    • 2012
  • Protein tyrosine phosphatase 1B (PTP1B) is important in the regulation of metabolic diseases and has emerged as a promising signaling target. Previously, we reported the PTP1B inhibitory activity of Rheum undulatum (RU). In the present study, we investigated the metabolic regulatory effects of RU in a high-fat diet (HFD) model. RU treatment significantly blocked body weight gain, which was accompanied by a reduction of feed efficiency. In addition, it led to a reduction of liver weight mediated by overexpression of PPAR${\alpha}$ and CPT1 in the liver, and an increase in the expression of adiponectin, aP2, and UCP3 in adipose tissue responsible for the reduction of total and LDL-cholesterol levels. Chrysophanol and physcion from RU significantly inhibited PTP1B activity and strongly enhanced insulin sensitivity. Altogether, our findings strongly suggest that 2 compounds are novel PTP1B inhibitors and might be considered as anti-obesity agents that are effective for suppressing body weight gain and improving lipid homeostasis.

계층 구조의 신경회로망에 의한 로보트 PTP 궤적 계획 (Robot PTP Trajectory Planning Using a Hierarchical Neural Network Structure)

  • 경계현;고명삼;이범희
    • 대한전기학회논문지
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    • 제39권10호
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    • pp.1121-1232
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    • 1990
  • A hierarchical neural network structure is described for robot PTP trajectory planning. In the first level, the multi-layered Perceptron neural network is used for the inverse kinematics with the back-propagation learning procedure. In the second level, a saccade generation model based joint trajectory planning model in proposed and analyzed with several features. Various simulations are performed to investigate the characteristics of the proposed neural networks.

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Screening of Protein Tyrosine Phosphatase 1B Inhibitory Activity from Some Vietnamese Medicinal Plants

  • Hoang, Duc Manh;Trung, Trinh Nam;Hien, Phan Thi Thu;Ha, Do Thi;Van Luong, Hoang;Lee, Myoung-Sook;Bae, Ki-Hwan
    • Natural Product Sciences
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    • 제16권4호
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    • pp.239-244
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    • 2010
  • Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling, has served as a potential drug target for the treatment of type 2 diabetes. The MeOH extracts of twenty-nine medicinal plants, traditionally used in Vietnam as anti-diabetes agents, were investigated for PTP1B inhibitory activity in vitro. The results indicated that, most materials showed moderate to strong inhibitory activity with $IC_{50}$ values ranging from $3.4\;{\mu}g/mL$ to $35.1\;{\mu}g/mL$; meanwhile, eleven extracts (37.9%) could demonstrate PTP1B activity with $IC_{50}$ values less than $15.5\;{\mu}g/mL$; sixteen extracts (55.2%) could demonstrate PTP1B activity with $IC_{50}$ values ranging from $15.5\;{\mu}g/mL$ to $35.1\;{\mu}g/mL$. The study may provide a proof, at least in a part, for the ethno-medical use in diabetes disease of these plants.

네트워크 본딩 기술을 기반한 IEEE 1588의 고장 허용 기술 연구 (Fault Tolerance for IEEE 1588 Based on Network Bonding)

  • 무스타파 알타하;이종명
    • 한국정보전자통신기술학회논문지
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    • 제11권4호
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    • pp.331-339
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    • 2018
  • IEEE 1588은 측정 및 제어 시스템에서 사용되는 네트워크의 정확한 시각 동기 표준(PTP, Precision Time Protocol)이다. Best Master Clock (BMC) 알고리즘은 PTP에서 최적의 마스터-슬레이브 계층을 선택하기 위해 사용한다. 슬레이브가 마스터와의 링크 장애 또는 현재의 시각 동기 에러가 발생하였을 때, BMC는 자동으로 다른 마스터 신호를 수신할 수 있도록 한다. 이때의 슬레이브 클럭은 마스터 신호의 장애 보상 시간 값에 따라 달라진다. 그러나 BMC 알고리즘에서는 마스터 클럭의 장애 발생에 따른 빠른 고장 복구 방안은 전혀 고려하지 않았다. 이에 본 논문에서는 네트워크 본딩 (Bonding) 기술을 적용하여 마스터 클럭의 장애에 따른 빠른 복구 방안을 제시하였다. 본 연구는 리눅스 시스템의 PTP livery 데몬(Ptpd)과 IEEE 1588의 특정 프로파일을 사용하였으며, 본딩 모드를 통해서 제어하도록 하였다. 네트워크 본딩 기술은 둘 이상의 네트워크 인터페이스 신호를 하나의 네트워크 인터페이스에 전송하기 위해 신호를 결합하는 과정에 대한 것으로, 네트워크의 이중화와 성능 향상을 제공한다. 본딩 기술은 만약 하나의 링크에서 장애가 발생하면, 본딩되어 있는 다른 링크를 통해서 즉각적으로 신호 전달이 가능하기에 네트워크의 이중화 또는 부하 분산 등에 사용한다. IEEE 1588만 적용한 것과 대비하여 IEEE 1588 기술과 네트워크 본딩 기술을 결합한 네트워크 복구 기술의 뛰어난 성능을 본 논문을 통하여 증명하였다.

Type 3 muscarinic acetylcholine receptor stimulation is a determinant of endothelial barrier function and adherens junctions integrity: role of protein-tyrosine phosphatase 1B

  • Jiao, Zhou-Yang;Wu, Jing;Liu, Chao;Wen, Bing;Zhao, Wen-Zeng;Du, Xin-Ling
    • BMB Reports
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    • 제47권10호
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    • pp.552-557
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    • 2014
  • The main purpose of this study was to investigate whether type 3 muscarinic acetylcholine receptor (M3R) dysfunction induced vascular hyperpermeability. Transwell system analysis showed that M3R inhibition by selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and small interfering RNA both increased endothelial permeability. Using coimmunoprecipitation and Western blot assay, we found that M3R inhibition increased VE-cadherin and ${\beta}$-catenin tyrosine phosphorylation without affecting their expression. Using PTP1B siRNA, we found that PTP1B was required for maintaining VE-cadherin and ${\beta}$-catenin protein dephosphorylation. In addition, 4-DAMP suppressed PTP1B activity by reducing cyclic adenosine monophosphate (cAMP), but not protein kinase $C{\alpha}$ ($PKC{\alpha}$). These data indicate that M3R preserves the endothelial barrier function through a mechanism potentially maintaining PTP1B activity, keeping the adherens junction proteins (AJPs) dephosphorylation.

IEEE 1588 PTP를 이용한 전파 지연 거리 측정의 정밀도 향상 기법 (Precision Improvement Technique of Propagation Delay Distance Measurement Using IEEE 1588 PTP)

  • 구영모;부정일;하정완;김복기
    • 한국항공우주학회지
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    • 제49권6호
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    • pp.515-519
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    • 2021
  • IEEE 1588 PTP는 두 시스템이 GPS의 도움 없이 송수신 시간 정보를 포함한 패킷을 주고받으면서 동기화하는 정밀 시각 프로토콜인데 시각 동기화 과정에서 전파 지연 시간을 계산하고 이를 이용하여 두 시스템 간의 거리를 측정할 수 있다. 본 논문에서는 수신 패킷의 프리앰블에서 추출한 타이밍 오류 정보를 이용하여 변조 심벌 주기 이하로 거리 측정 정밀도를 향상하는 방법을 제안하였다. 컴퓨터 시뮬레이션을 통해 거리 측정 정밀도는 프리앰블 PN 시퀀스의 길이와 신호대잡음비에 비례하는 것을 보였다.

Ginsenoside compound K reduces ischemia/reperfusion-induced neuronal apoptosis by inhibiting PTP1B-mediated IRS1 tyrosine dephosphorylation

  • Jing, Fu;Liang, Yu;Qian, Yu;Nengwei, Yu;Fei, Xu;Suping, Li
    • Journal of Ginseng Research
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    • 제47권2호
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    • pp.274-282
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    • 2023
  • Background: Ginsenoside compound K (CK) stimulated activation of the PI3K-Akt signaling is one of the major mechanisms in promoting cell survival after stroke. However, the underlying mediators remain poorly understood. This study aimed to explore the docking protein of ginsenoside CK mediating the neuroprotective effects. Materials and methods: Molecular docking, surface plasmon resonance, and cellular thermal shift assay were performed to explore ginsenoside CK interacting proteins. Neuroscreen-1 cells and middle cerebral artery occlusion (MCAO) model in rats were utilized as in-vitro and in-vivo models. Results: Ginsenoside CK interacted with recombinant human PTP1B protein and impaired its tyrosine phosphatase activity. Pathway and process enrichment analysis confirmed the involvement of PTP1B and its interacting proteins in PI3K-Akt signaling pathway. PTP1B overexpression reduced the tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) after oxygen-glucose deprivation/reoxygenation (OGD/R) in neuroscreen-1 cells. These regulations were confirmed in the ipsilateral ischemic hemisphere of the rat brains after MCAO/R. Ginsenoside CK treatment reversed these alterations and attenuated neuronal apoptosis. Conclusion: Ginsenoside CK binds to PTP1B with a high affinity and inhibits PTP1B-mediated IRS1 tyrosine dephosphorylation. This novel mechanism helps explain the role of ginsenoside CK in activating the neuronal protective PI3K-Akt signaling pathway after ischemia-reperfusion injury.

Ligand-Based Virtual Screening for inhibitors of PTP-1B with Antihyperglycemic properties

  • Kim, Heung-Jae;Yoo, Moo-Hi;Son, Mi-Won;Kim, Soon-Hoe
    • 대한약학회:학술대회논문집
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    • 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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    • pp.359.3-359.3
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    • 2002
  • Protein-tyrosine phosphatase 1 B(PTP-l B). which plays a key role in insulin signaling. is rising as a fascinating target for type 2 diabetes and obesity. Many scientists in structural biology solved the three dimensional X-ray Crystal structure of this type of enzyme, so we could easily get the active site structure of PTP-1 B or complex structure with ligand. Our virtual screening study for PTP-1B exactly based on these crystal strucutures from public database. (omitted)

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