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Comparison of three GPCR structural templates for modeling of the P2Y12 nucleotide receptor

Francesca Deflorian, Kenneth A. Jacobson
2011 Journal of Computer-Aided Molecular Design  
Three homology models of P2Y 12 R were compared, based on different GPCR structural templates: bovine rhodopsin (bRHO), human A 2A adenosine receptor (A 2A AR), and human C-X-C chemokine receptor type  ...  The P2Y 12 receptor (P2Y 12 R) is an ADP-activated G protein-coupled receptor (GPCR) that is an important target for antithrombotic drugs.  ...  David Erlinge (Lund University, Lund, Sweden) for helpful discussion. This research was supported by the Intramural Research Program of the NIH, NIDDK.  ... 
doi:10.1007/s10822-011-9423-3 pmid:21461952 pmcid:PMC3157290 fatcat:aoiwgjosxbc5rcli3tpoinir2e

GPCR-SSFE 2.0—a fragment-based molecular modeling web tool for Class A G-protein coupled receptors

Catherine L. Worth, Franziska Kreuchwig, Johanna K.S. Tiemann, Annika Kreuchwig, Michele Ritschel, Gunnar Kleinau, Peter W. Hildebrand, Gerd Krause
2017 Nucleic Acids Research  
Structural data of GPCRs are sparse yet important for elucidating the molecular basis of GPCR-related diseases and for performing structurebased drug design.  ...  Finally, blind-testing using two recently published structures shows that GPCR-SSFE 2.0 performs comparably or better than other state-of-the art GPCR modeling web servers.  ...  ACKNOWLEDGEMENTS We would like to thank members of the GLISTEN Cost action (CM1207) for helpful discussions.  ... 
doi:10.1093/nar/gkx399 pmid:28582569 pmcid:PMC5570183 fatcat:ozjdlhlmwvgx3kgw4sh5o6qity

Molecular modeling of the human P2Y14 receptor: A template for structure-based design of selective agonist ligands

Kevin Trujillo, Silvia Paoletta, Evgeny Kiselev, Kenneth A. Jacobson
2015 Bioorganic & Medicinal Chemistry  
The P2Y14R model supports the hypothesis of a conserved binding mode of nucleotides in the three P2Y12-like receptors involving functionally conserved residues.  ...  analogues and to probe the quality of P2Y14R homology modeling as a template for structure-based design.  ...  Acknowledgements Funding from the NIH Undergraduate Scholarship Program (UGSP) to KT, the NIGMS Postdoctoral Research Associate (PRAT) program to EK and the Intramural Research Program of NIDDK (Z01 DK031126  ... 
doi:10.1016/j.bmc.2015.03.042 pmid:25868749 pmcid:PMC4468048 fatcat:ydgledln7fcrfmypzn3tz66nei

GPCRM: a homology modeling web service with triple membrane-fitted quality assessment of GPCR models

Przemysław Miszta, Paweł Pasznik, Jakub Jakowiecki, Agnieszka Sztyler, Dorota Latek, Sławomir Filipek
2018 Nucleic Acids Research  
Therefore, the need for new, high quality structures of GPCRs is enormous.  ...  Additionally, due to three different scoring functions (Rosetta, Rosetta-MP, BCL::Score) it is possible to select accurate models for the required purposes: the structure of the binding site, the transmembrane  ...  ACKNOWLEDGEMENTS The European COST Action CM1207 (GLISTEN) for providing biannual forum for exchange ideas on GPCR research and for supporting mutual visits.  ... 
doi:10.1093/nar/gky429 pmid:29788177 pmcid:PMC6030973 fatcat:tirmcb2ponc35igw3ag7h34wfq

Application of GPCR Structures for Modelling of Free Fatty Acid Receptors [chapter]

Irina G. Tikhonova
2016 Handbook of Experimental Pharmacology  
The recent progress in crystallography of GPCRs has now enabled the elucidation of the structure of FFA1 and provided reliable templates for homology modelling of other FFA receptors.  ...  Analysis of the crystal structure and improved homology models, along with mutagenesis data and structure activity, highlighted an unusual arginine charge pairing interaction in FFA1-3 for receptor modulation  ...  Recent advances in structural biology of GPCRs have provided alternative templates for homology modelling of GPR120.  ... 
doi:10.1007/164_2016_52 pmid:27757764 fatcat:2vno7b6omfbobjdq2vdifqsb74

Membrane Environment Modulates Ligand-Binding Propensity of P2Y12 Receptor

Fatemeh Haghighi, Semen Yesylevskyy, Siamak Davani, Christophe Ramseyer
2021 Pharmaceutics  
In this work, we performed all-atom molecular dynamics simulations of the full-length P2Y12 receptor in three different membrane environments and in two possible conformations derived from available crystal  ...  The binding of natural ligands and synthetic drugs to the P2Y12 receptor is of great interest because of its crucial role in platelets activation and the therapy of arterial thrombosis.  ...  The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.  ... 
doi:10.3390/pharmaceutics13040524 pmid:33918934 pmcid:PMC8069422 fatcat:rcoq6ofzibffho6bpl5xn4gj74

Agonists and antagonists for P2 receptors

Kenneth A Jacobson, Stefano Costanzi, Bhalchandra V Joshi, Pedro Besada, Dae Hong Shin, Hyojin Ko, Andrei A Ivanov, Liaman Mamedova
2006 Novartis Foundation symposium  
Three-dimensional structures of P2Y receptors have been deduced from structure activity relationships (SAR), mutagenesis and modelling studies.  ...  Detailed three-dimensional structures of P2X receptors have not yet been proposed.  ...  Jacobson: We don't yet have a good template for modelling the activated form of the receptor, so we can't adequately answer that question.  ... 
pmid:16805423 pmcid:PMC4321821 fatcat:wmpad242vrbobnicfhdl37atdy

A Novel Gαq/11-selective Inhibitor

Jun Takasaki, Tetsu Saito, Masatoshi Taniguchi, Tomihisa Kawasaki, Yumiko Moritani, Kazumi Hayashi, Masato Kobori
2004 Journal of Biological Chemistry  
These suggested that the acting point of YM-254890 is receptor-G␣ q interaction or the subsequent guanine nucleotide exchange step.  ...  These data indicate that YM-254890 blocks the exchange of GDP for GTP in G␣ q/11 activation.  ...  Nagata for providing the pEF-BOS vector.  ... 
doi:10.1074/jbc.m408846200 pmid:15339913 fatcat:f2tsu72ffzh2dlbjvyxt6n4cju

Structure of the human P2Y12 receptor in complex with an antithrombotic drug

Kaihua Zhang, Jin Zhang, Zhan-Guo Gao, Dandan Zhang, Lan Zhu, Gye Won Han, Steven M. Moss, Silvia Paoletta, Evgeny Kiselev, Weizhen Lu, Gustavo Fenalti, Wenru Zhang (+9 others)
2014 Nature  
P2Y receptors (P2YRs), a family of purinergic G-protein-coupled receptors (GPCRs), are activated by extracellular nucleotides.  ...  For receptors other than P2Y 12 R, only helix VI is shown, and the residues at position 6.48 are shown as sticks. f, The comparison of ligand-binding sites of GPCRs from α (β 2 AR and A 2A AR), β (NTSR1  ... 
doi:10.1038/nature13083 pmid:24670650 pmcid:PMC4174307 fatcat:ymf4oa7xdngznogufsndeeblju

Structure-Based Sequence Alignment of the Transmembrane Domains of All Human GPCRs: Phylogenetic, Structural and Functional Implications

Vaclav Cvicek, William A. Goddard, Ravinder Abrol, Nir Ben-Tal
2016 PLoS Computational Biology  
The GRoSS alignment also enables the quantification of the structural variability in the TM regions of experimental structures, useful for homology modeling and structure prediction of receptors.  ...  The understanding of G-protein coupled receptors (GPCRs) is undergoing a revolution due to increased information about their signaling and the experimental determination of structures for more than 25  ...  Soo-Kyung Kim Author Contributions Conceived and designed the experiments: RA VC WAG. Performed the experiments: VC. Analyzed the data: VC WAG RA. Wrote the paper: VC WAG RA.  ... 
doi:10.1371/journal.pcbi.1004805 pmid:27028541 pmcid:PMC4814114 fatcat:2nyt5demwng5jalbs6lceyq4si

Discovery and validation of potential drug targets based on the phylogenetic evolution of GPCRs

Jie Yang, Sen Li, Tong-Yang Zhu, Xiao-Ning Wang, Zhen Zhang
2012 Natural Science  
G-protein coupled recaptors (GPCRs) are among the most important drug targets for the pharmaceutical industry.  ...  Some scoring matrices were trained on 22 groups of GPCRs in the GPCRDB database. These models were employed to predict the GPCR proteins in two groups of test sets.  ...  . human ADP receptor (Purinergic Receptor P2Y12) [40] , are constructed by homology modeling using bovine rhodopsin as a template.  ... 
doi:10.4236/ns.2012.412a139 fatcat:emfa5fffanba5hwdtoktnmb65a

Mapping Human Protease-activated Receptor 4 (PAR4) Homodimer Interface to Transmembrane Helix 4

María de la Fuente, Daniel N. Noble, Sheetal Verma, Marvin T. Nieman
2012 Journal of Biological Chemistry  
Conclusion: Dimerization of PAR4 is critical for signaling. Significance: The interactions of PAR4 at the plasma membrane may have important functions that regulate signaling.  ...  Because of the importance of PAR4 activation on platelets in humans and mice and emerging roles for PAR4 in other tissues, experiments were done to characterize the interaction between PAR4 homodimers.  ...  Acknowledgments-We thank Michele Mumaw and Amal Arachiche for helpful suggestions and editing of the manuscript.  ... 
doi:10.1074/jbc.m112.341438 pmid:22318735 pmcid:PMC3322995 fatcat:aa4hklz5dndinjv3qlojuqnvnq

A chemogenomic analysis of the transmembrane binding cavity of human G-protein-coupled receptors

Jean-Sebastien Surgand, Jordi Rodrigo, Esther Kellenberger, Didier Rognan
2005 Proteins: Structure, Function, and Bioinformatics  
the X-ray structure of bovine rhodopsin bound to retinal-to line the TM binding cavity of ground-state receptors.  ...  The current approach allows a very fast comparison of most human GPCRs from the focused perspective of the predicted TM cavity and permits to easily detect key residues that drive ligand selectivity or  ...  reduced set of templates used for comparative modelling, the modeled TM cavity of most GPCRs share significant similarities, notably the presence of two subsites, a first one delimited by TMs 1, 2, 3,  ... 
doi:10.1002/prot.20768 pmid:16294340 fatcat:fu3onxrzyvci3kk7tbus2gre7i

Extracellular mRNA Induces Dendritic Cell Activation by Stimulating Tumor Necrosis Factor-α Secretion and Signaling through a Nucleotide Receptor

Houping Ni, John Capodici, Georgetta Cannon, Didier Communi, Jean-Marie Boeynaems, Katalin Karikó, Drew Weissman
2002 Journal of Biological Chemistry  
P2Y type nucleotide receptor.  ...  The role of this signaling activity in vaccine design and the potential effect of mRNA released by damaged cells in the induction of immune responsiveness is discussed.  ...  Skip Brass for the use of his fluorescence spectrophotometer.  ... 
doi:10.1074/jbc.m110729200 pmid:11821398 fatcat:yxqt52gmezdhtb7l23dn7datz4

G protein-coupled receptors: the evolution of structural insight

Samantha B. Gacasan, Daniel L. Baker, Abby L. Parrill
2017 AIMS Biophysics  
Although these receptors have been investigated for decades, three-dimensional structures of GPCR have only recently become available.  ...  These efforts have resulted in the determination of three-dimensional structures for over 40 individual GPCR family members.  ...  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.  ... 
doi:10.3934/biophy.2017.3.491 pmid:29951585 pmcid:PMC6018013 fatcat:atpu2cbt3nbqfi3pnflk55bpnm
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