ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-01-08
    Description: G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the beta(2) adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805469/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805469/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bokoch, Michael P -- Zou, Yaozhong -- Rasmussen, Soren G F -- Liu, Corey W -- Nygaard, Rie -- Rosenbaum, Daniel M -- Fung, Juan Jose -- Choi, Hee-Jung -- Thian, Foon Sun -- Kobilka, Tong Sun -- Puglisi, Joseph D -- Weis, William I -- Pardo, Leonardo -- Prosser, R Scott -- Mueller, Luciano -- Kobilka, Brian K -- GM56169/GM/NIGMS NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- R01 GM056169/GM/NIGMS NIH HHS/ -- R01 GM056169-13/GM/NIGMS NIH HHS/ -- R21 MH082313/MH/NIMH NIH HHS/ -- R21 MH082313-01A1/MH/NIMH NIH HHS/ -- R37 NS028471/NS/NINDS NIH HHS/ -- R37 NS028471-19/NS/NINDS NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):108-12. doi: 10.1038/nature08650.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054398" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-2 Receptor Agonists ; Adrenergic beta-2 Receptor Antagonists ; Allosteric Regulation/drug effects ; Binding Sites ; Crystallography, X-Ray ; Drug Inverse Agonism ; Ethanolamines/pharmacology ; Formoterol Fumarate ; Humans ; Ligands ; Lysine/analogs & derivatives/metabolism ; Methylation ; Models, Molecular ; Mutant Proteins ; Nuclear Magnetic Resonance, Biomolecular ; Propanolamines/metabolism/pharmacology ; Protein Structure, Tertiary/drug effects ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism ; Static Electricity ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Structure of the delta-opioid receptor bound to naltrindole (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-05-19
    Description: The opioid receptor family comprises three members, the micro-, delta- and kappa-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The delta-opioid receptor (delta-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood. The structures of the micro-OR and kappa-OR have recently been solved. Here we report the crystal structure of the mouse delta-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the micro-OR and kappa-OR, the delta-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology, in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the delta-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523198/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523198/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Granier, Sebastien -- Manglik, Aashish -- Kruse, Andrew C -- Kobilka, Tong Sun -- Thian, Foon Sun -- Weis, William I -- Kobilka, Brian K -- DA031418/DA/NIDA NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- R01 GM083118/GM/NIGMS NIH HHS/ -- R01 NS028471/NS/NINDS NIH HHS/ -- R21 DA031418/DA/NIDA NIH HHS/ -- England -- Nature. 2012 May 16;485(7398):400-4. doi: 10.1038/nature11111.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA. granier@stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22596164" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Binding Sites ; Conserved Sequence ; Crystallography, X-Ray ; Mice ; Models, Molecular ; Molecular Sequence Data ; Naltrexone/*analogs & derivatives/chemistry/metabolism/pharmacology ; Protein Structure, Tertiary ; Receptors, Opioid, delta/antagonists & inhibitors/*chemistry/metabolism ; Reproducibility of Results ; Structure-Activity Relationship ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-01-14
    Description: G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human beta(2) adrenergic receptor (beta(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive beta(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 A outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058308/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058308/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rasmussen, Soren G F -- Choi, Hee-Jung -- Fung, Juan Jose -- Pardon, Els -- Casarosa, Paola -- Chae, Pil Seok -- Devree, Brian T -- Rosenbaum, Daniel M -- Thian, Foon Sun -- Kobilka, Tong Sun -- Schnapp, Andreas -- Konetzki, Ingo -- Sunahara, Roger K -- Gellman, Samuel H -- Pautsch, Alexander -- Steyaert, Jan -- Weis, William I -- Kobilka, Brian K -- GM083118/GM/NIGMS NIH HHS/ -- GM56169/GM/NIGMS NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- P01 GM75913/GM/NIGMS NIH HHS/ -- P60DK-20572/DK/NIDDK NIH HHS/ -- R01 GM068603/GM/NIGMS NIH HHS/ -- R01 GM083118/GM/NIGMS NIH HHS/ -- R01 GM083118-04/GM/NIGMS NIH HHS/ -- R37 NS028471/NS/NINDS NIH HHS/ -- R37 NS028471-21/NS/NINDS NIH HHS/ -- England -- Nature. 2011 Jan 13;469(7329):175-80. doi: 10.1038/nature09648.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21228869" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-2 Receptor ; Agonists/*chemistry/immunology/metabolism/*pharmacology ; Animals ; Binding Sites ; Camelids, New World ; Crystallography, X-Ray ; Drug Inverse Agonism ; Humans ; Immunoglobulin Fragments/*chemistry/*immunology/metabolism/pharmacology ; Ligands ; Models, Molecular ; Movement/drug effects ; Nanostructures/*chemistry ; Opsins/agonists/chemistry/metabolism ; Propanolamines/chemistry/metabolism/pharmacology ; Protein Conformation/drug effects ; Protein Stability/drug effects ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism ; Viral Proteins/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    Crystal structure of the beta2 adrenergic receptor-Gs protein complex (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-07-21
    Description: G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The beta(2) adrenergic receptor (beta(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric beta(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the beta(2)AR and Gs involve the amino- and carboxy-terminal alpha-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the beta(2)AR include a 14 A outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an alpha-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the alpha-helical domain of Galphas relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184188/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184188/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rasmussen, Soren G F -- DeVree, Brian T -- Zou, Yaozhong -- Kruse, Andrew C -- Chung, Ka Young -- Kobilka, Tong Sun -- Thian, Foon Sun -- Chae, Pil Seok -- Pardon, Els -- Calinski, Diane -- Mathiesen, Jesper M -- Shah, Syed T A -- Lyons, Joseph A -- Caffrey, Martin -- Gellman, Samuel H -- Steyaert, Jan -- Skiniotis, Georgios -- Weis, William I -- Sunahara, Roger K -- Kobilka, Brian K -- GM083118/GM/NIGMS NIH HHS/ -- GM56169/GM/NIGMS NIH HHS/ -- GM75915/GM/NIGMS NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- P01 GM75913/GM/NIGMS NIH HHS/ -- P50GM073210/GM/NIGMS NIH HHS/ -- P60DK-20572/DK/NIDDK NIH HHS/ -- R01 GM068603/GM/NIGMS NIH HHS/ -- R01 GM068603-01/GM/NIGMS NIH HHS/ -- R01 GM068603-02/GM/NIGMS NIH HHS/ -- R01 GM068603-03/GM/NIGMS NIH HHS/ -- R01 GM068603-04/GM/NIGMS NIH HHS/ -- R01 GM068603-05/GM/NIGMS NIH HHS/ -- T32-GM008270/GM/NIGMS NIH HHS/ -- U54 GM094599/GM/NIGMS NIH HHS/ -- U54GM094599/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Jul 19;477(7366):549-55. doi: 10.1038/nature10361.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21772288" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-2 Receptor Agonists/chemistry/metabolism ; Animals ; Catalytic Domain ; Cattle ; Crystallization ; Crystallography, X-Ray ; Enzyme Activation ; GTP-Binding Protein alpha Subunits, Gs/*chemistry/*metabolism ; Models, Molecular ; Multiprotein Complexes/chemistry/metabolism ; Protein Binding ; Rats ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    Crystal structure of the micro-opioid receptor bound to a morphinan antagonist (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-03-23
    Description: Opium is one of the world's oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many undesirable side effects (sedation, apnoea and dependence) by binding to and activating the G-protein-coupled micro-opioid receptor (micro-OR) in the central nervous system. Here we describe the 2.8 A crystal structure of the mouse micro-OR in complex with an irreversible morphinan antagonist. Compared to the buried binding pocket observed in most G-protein-coupled receptors published so far, the morphinan ligand binds deeply within a large solvent-exposed pocket. Of particular interest, the micro-OR crystallizes as a two-fold symmetrical dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6. These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523197/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523197/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manglik, Aashish -- Kruse, Andrew C -- Kobilka, Tong Sun -- Thian, Foon Sun -- Mathiesen, Jesper M -- Sunahara, Roger K -- Pardo, Leonardo -- Weis, William I -- Kobilka, Brian K -- Granier, Sebastien -- DA031418/DA/NIDA NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- R01 GM083118/GM/NIGMS NIH HHS/ -- R01 NS028471/NS/NINDS NIH HHS/ -- R21 DA031418/DA/NIDA NIH HHS/ -- England -- Nature. 2012 Mar 21;485(7398):321-6. doi: 10.1038/nature10954.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22437502" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Crystallography, X-Ray ; Ligands ; Mice ; Models, Molecular ; Morphinans/*chemistry/metabolism/pharmacology ; Protein Conformation ; Protein Multimerization ; Receptors, Opioid, mu/*antagonists & inhibitors/*chemistry/metabolism ; Solvents/chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-10-27
    Description: Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human beta2-adrenergic receptor-T4 lysozyme fusion protein bound to the partial inverse agonist carazolol at 2.4 angstrom resolution. The structure provides a high-resolution view of a human G protein-coupled receptor bound to a diffusible ligand. Ligand-binding site accessibility is enabled by the second extracellular loop, which is held out of the binding cavity by a pair of closely spaced disulfide bridges and a short helical segment within the loop. Cholesterol, a necessary component for crystallization, mediates an intriguing parallel association of receptor molecules in the crystal lattice. Although the location of carazolol in the beta2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopsin as a template model for this large receptor family.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583103/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583103/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cherezov, Vadim -- Rosenbaum, Daniel M -- Hanson, Michael A -- Rasmussen, Soren G F -- Thian, Foon Sun -- Kobilka, Tong Sun -- Choi, Hee-Jung -- Kuhn, Peter -- Weis, William I -- Kobilka, Brian K -- Stevens, Raymond C -- F32 GM082028/GM/NIGMS NIH HHS/ -- GM075915/GM/NIGMS NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- P50 GM062411/GM/NIGMS NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073197-04/GM/NIGMS NIH HHS/ -- R01 GM056169/GM/NIGMS NIH HHS/ -- R01 GM089857/GM/NIGMS NIH HHS/ -- R21 GM075811/GM/NIGMS NIH HHS/ -- U54 GM074961/GM/NIGMS NIH HHS/ -- U54 GM074961-030001/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 23;318(5854):1258-65. Epub 2007 Oct 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17962520" target="_blank"〉PubMed〈/a〉
    Keywords: Bacteriophage T4/enzymology ; Binding Sites ; Cell Membrane/chemistry/metabolism ; Cholesterol/chemistry/metabolism ; Crystallization ; Crystallography, X-Ray ; Drug Inverse Agonism ; Humans ; Ligands ; Models, Molecular ; Muramidase/chemistry/metabolism ; Propanolamines/chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Receptors, Adrenergic, beta-2/*chemistry/metabolism ; Recombinant Fusion Proteins/chemistry/metabolism ; Rhodopsin/chemistry/metabolism ; Static Electricity
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-10-27
    Description: The beta2-adrenergic receptor (beta2AR) is a well-studied prototype for heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) that respond to diffusible hormones and neurotransmitters. To overcome the structural flexibility of the beta2AR and to facilitate its crystallization, we engineered a beta2AR fusion protein in which T4 lysozyme (T4L) replaces most of the third intracellular loop of the GPCR ("beta2AR-T4L") and showed that this protein retains near-native pharmacologic properties. Analysis of adrenergic receptor ligand-binding mutants within the context of the reported high-resolution structure of beta2AR-T4L provides insights into inverse-agonist binding and the structural changes required to accommodate catecholamine agonists. Amino acids known to regulate receptor function are linked through packing interactions and a network of hydrogen bonds, suggesting a conformational pathway from the ligand-binding pocket to regions that interact with G proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosenbaum, Daniel M -- Cherezov, Vadim -- Hanson, Michael A -- Rasmussen, Soren G F -- Thian, Foon Sun -- Kobilka, Tong Sun -- Choi, Hee-Jung -- Yao, Xiao-Jie -- Weis, William I -- Stevens, Raymond C -- Kobilka, Brian K -- F32 GM082028/GM/NIGMS NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM62411/GM/NIGMS NIH HHS/ -- R01 GM056169/GM/NIGMS NIH HHS/ -- R21 GM075811/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 23;318(5854):1266-73. Epub 2007 Oct 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17962519" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenergic beta-Agonists/chemistry/metabolism ; Adrenergic beta-Antagonists/chemistry/metabolism ; Amino Acid Sequence ; Bacteriophage T4/enzymology ; Binding Sites ; Cell Line ; Cell Membrane/chemistry/metabolism ; Crystallization ; Crystallography, X-Ray ; Drug Inverse Agonism ; Humans ; Immunoglobulin Fab Fragments/chemistry/metabolism ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Muramidase/chemistry/metabolism ; Propanolamines/chemistry/metabolism ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism ; Recombinant Fusion Proteins/chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    Crystal structures of the M1 and M4 muscarinic acetylcholine receptors (2016)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2016-03-10
    Description: Muscarinic M1-M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In particular, the M1 and M4 receptor subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzheimer's disease and schizophrenia, but the high conservation of the acetylcholine-binding pocket has spurred current research into targeting allosteric sites on these receptors. Here we report the crystal structures of the M1 and M4 muscarinic receptors bound to the inverse agonist, tiotropium. Comparison of these structures with each other, as well as with the previously reported M2 and M3 receptor structures, reveals differences in the orthosteric and allosteric binding sites that contribute to a role in drug selectivity at this important receptor family. We also report identification of a cluster of residues that form a network linking the orthosteric and allosteric sites of the M4 receptor, which provides new insight into how allosteric modulation may be transmitted between the two spatially distinct domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thal, David M -- Sun, Bingfa -- Feng, Dan -- Nawaratne, Vindhya -- Leach, Katie -- Felder, Christian C -- Bures, Mark G -- Evans, David A -- Weis, William I -- Bachhawat, Priti -- Kobilka, Tong Sun -- Sexton, Patrick M -- Kobilka, Brian K -- Christopoulos, Arthur -- U19 GM106990/GM/NIGMS NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Mar 17;531(7594):335-40. doi: 10.1038/nature17188. Epub 2016 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Drug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, Victoria, Australia. ; ConfometRx, 3070 Kenneth Street, Santa Clara, California 95054, USA. ; Neuroscience, Eli Lilly, Indianapolis, Indiana 46285, USA. ; Computational Chemistry and Chemoinformatics, Eli Lilly, Indianapolis, Indiana 46285, USA. ; Computational Chemistry and Chemoinformatics, Eli Lilly, Sunninghill Road, Windlesham GU20 6PH, UK. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26958838" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylcholine/metabolism ; Allosteric Regulation/drug effects ; Allosteric Site/drug effects ; Alzheimer Disease ; Crystallization ; Crystallography, X-Ray ; Drug Inverse Agonism ; Humans ; Models, Molecular ; Nicotinic Acids/metabolism/pharmacology ; Receptor, Muscarinic M1/*chemistry/metabolism ; Receptor, Muscarinic M4/*chemistry/metabolism ; Schizophrenia ; Static Electricity ; Substrate Specificity ; Surface Properties ; Thiophenes/metabolism/pharmacology ; Tiotropium Bromide/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor (1987)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1987-10-30
    Description: The gene for the human platelet alpha 2-adrenergic receptor has been cloned with oligonucleotides corresponding to the partial amino acid sequence of the purified receptor. The identity of this gene has been confirmed by the binding of alpha 2-adrenergic ligands to the cloned receptor expressed in Xenopus laevis oocytes. The deduced amino acid sequence is most similar to the recently cloned human beta 2- and beta 1-adrenergic receptors; however, similarities to the muscarinic cholinergic receptors are also evident. Two related genes have been identified by low stringency Southern blot analysis. These genes may represent additional alpha 2-adrenergic receptor subtypes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kobilka, B K -- Matsui, H -- Kobilka, T S -- Yang-Feng, T L -- Francke, U -- Caron, M G -- Lefkowitz, R J -- Regan, J W -- New York, N.Y. -- Science. 1987 Oct 30;238(4827):650-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2823383" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Blood Platelets/*physiology ; Cloning, Molecular ; GTP-Binding Proteins/metabolism ; Gene Expression Regulation ; Genes ; Humans ; Infant, Newborn ; Membrane Proteins/*genetics ; Molecular Sequence Data ; Multigene Family ; Oligodeoxyribonucleotides ; Phosphoproteins/genetics ; Receptors, Adrenergic, alpha/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Chimeric alpha 2-,beta 2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity (1988)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1988-06-03
    Description: The alpha 2 and beta 2 adrenergic receptors, both of which are activated by epinephrine, but which can be differentiated by selective drugs, have opposite effects (inhibitory and stimulatory) on the adenylyl cyclase system. The two receptors are homologous with each other, rhodopsin, and other receptors coupled to guanine nucleotide regulatory proteins and they contain seven hydrophobic domains, which may represent transmembrane spanning segments. The function of specific structural domains of these receptors was determined after construction and expression of a series of chimeric alpha 2-,beta 2-adrenergic receptor genes. The specificity for coupling to the stimulatory guanine nucleotide regulatory protein lies within a region extending from the amino terminus of the fifth hydrophobic domain to the carboxyl terminus of the sixth. Major determinants of alpha 2- and beta 2-adrenergic receptor agonist and antagonist ligand binding specificity are contained within the seventh membrane spanning domain. Chimeric receptors should prove useful for elucidating the structural basis of receptor function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kobilka, B K -- Kobilka, T S -- Daniel, K -- Regan, J W -- Caron, M G -- Lefkowitz, R J -- HL 16037/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1988 Jun 3;240(4857):1310-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2836950" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Chimera ; Cloning, Molecular ; GTP-Binding Proteins/metabolism ; Humans ; Molecular Sequence Data ; Pindolol/analogs & derivatives/metabolism ; Protein Conformation ; Receptors, Adrenergic, alpha/*genetics ; Receptors, Adrenergic, beta/*genetics ; Yohimbine/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...