• Title/Summary/Keyword: PtpA

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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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    • v.35 no.6
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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.

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

  • Kim, Seong-Jin;Ko, Kwang-Man
    • The KIPS Transactions:PartA
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    • v.19A no.4
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    • pp.181-186
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    • 2012
  • The distributed measurement and control system require technology to solve complex synchronization problem among distributed devices. It can be solved by using IEEE Standard for a Precision Clock Synchronization Protocol for Networked Measurement and Control Systems to synchronize real-time clocks incorporated within each component of the system. In this paper, we implemented the IEEE 1588v2 PTP emulator on BlueScope BL6000A using a delay request-response mechanism to measure clock synchronization.

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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    • v.45 no.3
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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.

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

  • 경계현;고명삼;이범희
    • The Transactions of the Korean Institute of Electrical Engineers
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    • v.39 no.10
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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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    • v.16 no.4
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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.

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

  • Altaha, Mustafa;Rhee, Jong Myung
    • The Journal of Korea Institute of Information, Electronics, and Communication Technology
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    • v.11 no.4
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    • pp.331-339
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    • 2018
  • The IEEE 1588, commonly known as a precision time protocol (PTP), is a standard for precise clock synchronization that maintains networked measurements and control systems. The best master clock (BMC) algorithm is currently used to establish the master-slave hierarchy for PTP. The BMC allows a slave clock to automatically take over the duties of the master when the slave is disconnected due to a link failure and loses its synchronization; the slave clock depends on a timer to compensate for the failure of the master. However, the BMC algorithm does not provide a fast recovery mechanism in the case of a master failure. In this paper, we propose a technique that combines the IEEE 1588 with network bonding to provide a faster recovery mechanism in the case of a master failure. This technique is implemented by utilizing a pre-existing library PTP daemon (Ptpd) in Linux system, with a specific profile of the IEEE 1588 and it's controlled through bonding modes. Network bonding is a process of combining or joining two or more network interfaces together into a single interface. Network bonding offers performance improvements and redundancy. If one link fails, the other link will work immediately. It can be used in situations where fault tolerance, redundancy, or load balancing networks are needed. The results show combining IEEE 1588 with network bonding enables an incredible shorter recovery time than simply just relying on the IEEE 1588 recovery method alone.

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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    • v.47 no.10
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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.

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

  • Gu, Young Mo;Boo, Jung-il;Ha, Jeong-wan;Kim, Bokki
    • Journal of the Korean Society for Aeronautical & Space Sciences
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    • v.49 no.6
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    • pp.515-519
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    • 2021
  • IEEE 1588 PTP is a precision time protocol in which two systems synchronize without the aid of GPS by exchanging packets including transmission/reception time information. In the time synchronization process, the propagation delay time can be calculated and the distance between the two systems can be measured using this. In this paper, we proposed a method to improve the distance measurement precision less than the modulation symbol period using the timing error information extracted from the preamble of the received packet. Computer simulations show that the distance measurement precision is proportional to the length of the preamble PN sequence and the signal-to-noise ratio.

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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    • v.47 no.2
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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
    • Proceedings of the PSK Conference
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    • 2002.10a
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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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