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https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Nikki+Hunter Proteopedia - User contributions [en] 2026-09-16T05:07:17Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=Membrane_proteins&diff=1867216 Membrane proteins 2013-11-21T19:09:04Z

<p>Nikki Hunter: /* See Also */</p> <hr /> <div>==Proteopedia Articles==<br /> * [[Photosystem II]]<br /> *Escherichia coli GlpG, an integral membrane protein rhomboid protease, unique in cleaving the transmembrane domains of other membrane proteins, [[2ic8]].<br /> *[[Ion channels]]<br /> *[[Pore forming toxin, α-hemolysin]]<br /> *[[Urea transporter]]<br /> *[[Ionotropic Glutamate Receptor|Glutamate receptor]]<br /> *[[G protein-coupled receptor|G protein-coupled receptors]]<br /> *[[A Physical Model of the β2-Adrenergic Receptor ]]<br /> <br /> ==See Also==<br /> * [[Secondary structure]]<br /> * [[Ligand Binding N-Terminal of Metabotropic Glutamate Receptors]]<br /> <br /> ==External Resources==<br /> *[http://blanco.biomol.uci.edu/Membrane_Proteins_xtal.html Membrane Proteins of Known 3D Structure] (from the Stephen White laboratory at Univ. California, Irvine, USA).<br /> *[http://www.mpibp-frankfurt.mpg.de/michel/public/memprotstruct.html Membrane Proteins of Known Structure] (from Max Planck Institute in Frankfurt, Germany) not updated since 2006 but useful for tabulation of crystallization conditions.<br /> *[http://opm.phar.umich.edu/ Orientations of Proteins in Membranes (OPM) database] (University of Michigan, USA) features calculated membrane boundaries for all membrane proteins in the PDB.<br /> * [http://bioinf.cs.ucl.ac.uk/psipred/ The PSIPRED Protein Structure Prediction Server] has a highly accurate method for protein secondary structure prediction for proteins without an empirically-determined 3D structure and features also a widely used transmembrane topology prediction method where the output includes a Kyte-Doolittle Hydropathy Plot. <br /> <ref group="xtra">PMID: 17139331</ref><references group="xtra"/></div>

Nikki Hunter https://proteopedia.org/index.php?title=G_protein-coupled_receptor&diff=1867215 G protein-coupled receptor 2013-11-21T19:08:20Z

<p>Nikki Hunter: /* See Also */</p> <hr /> <div>[[G protein-coupled receptor|G protein-coupled receptors]], often abbreviated GPCRs, are an abundant superfamily of proteins also known as [[G protein-coupled receptor|seven-transmembrane domain receptors]], [[G protein-coupled receptor|7TM receptors]], [[G protein-coupled receptor|7 pass transmembrane receptors]], [[G protein-coupled receptor|heptahelical receptors]], [[G protein-coupled receptor|serpentine receptor]], and [[G protein-coupled receptor|G protein-linked receptors (GPLRs)]]. [[G protein-coupled receptor|G protein-coupled receptors]] are cell surface signalling proteins involved in many physiological functions and in multiple diseases. They are also the target of the majority of all modern [[Pharmaceutical Drugs|medicinal drugs]]<ref name="howmany">PMID: 17139284</ref><ref name="pharmtrends">PMID: 21075459</ref>. The extracellular side is generally where the ligand enters for binding. On the intracellular side they interact with [[GTP-binding protein| G proteins]] involved in signaling induced by the binding of the ligand.<br /> <br /> Illustrating their importance and the largesse of the superfamily, there are roughly 800 known members of the superfamily in the human genome alone — estimated to be 4% of human protein-coding genes. Members are further subclassified into one of five families of GPCRs<ref>PMID: 20019124</ref>.<br /> <br /> Rhodopsin shares similar membrane topology with the members of the superfamily, specifically family A of the [[G protein-coupled receptor|G protein-coupled receptors]] which include the seven transmembrane helices, an extracellular N-terminus and cytoplasmic C-terminus<ref name="rhodopsin">PMID:15251227</ref>.<br /> <br /> [[Image:7tm labeled.png|right|400px]]<br /> ==3D Structures of G protein-coupled receptors==<br /> <br /> ===Rhodopsins===<br /> Rhodopsins are listed individually [[Rhodopsin#3D structures of rhodopsin|in a section on the Rhodopsin topic page]]<br /> 3D structures in [[Rhodopsin]].<br /> <br /> ===β2 adrenergic receptor===<br /> {{Template:GPCR3sn6}}<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> * A [[Beta-2 Adrenergic Receptor|topic page]] concerning the [[Beta-2 Adrenergic Receptor]]<br /> * The human β2 adrenergic receptor bound to a G-protein ([[3sn6]]) is featured in a scene on the right, and additional structures are on the [[Adrenergic receptor|Adrenergic receptor page]].<br /> <br /> ===β1 adrenergic receptor===<br /> 3D structures in [[Adrenergic receptor]].<br /> <br /> ===A2A adenosine receptor===<br /> * [[3eml]] - human A2A adenosine receptor bound to antagaonist ZM241385<br /> * [[3pwh]] - thermostabilized human A2A adenosine receptor<br /> * [[3rey]] - thermostabilized human A2A adenosine receptor in complex with the xanthines xanthine amine congener<br /> * [[3rfm]] - thermostabilized human A2A adenosine receptor in complex with caffeine<br /> * [[3qak]] - human A2A adenosine receptor bound to an agonist UK-432097<br /> * [[3vg9]] - human A2A adenosine receptor in complex with a mouse monoclonal-antibody Fab fragment, Fab2838<br /> * [[3vga]] - human A2A adenosine receptor in complex with a mouse monoclonal-antibody Fab fragment, Fab2838<br /> * [[2yd0]] - human A2A adenosine receptor in complex with the endogenous agonist adenosine<br /> * [[2ydv]] - human A2A adenosine receptor in complex with synthetic agonist NECA<br /> * [[4eiy]] - human A2A adenosine receptor thermostabilized by replacing its third intracellular loop with apocytochrome b(562)RIL<br /> <br /> ===Histamine H1 receptor===<br /> * [[3rze]] - human histamine H1 receptor<br /> <br /> ===Sphingosine 1-phosphate Receptor===<br /> * [[3v2w]],[[3v2y]] - human sphingosine 1-phosphate receptor 1 with a bound sphingolipid mimic<br /> <br /> ===Dopamine D3 Receptor===<br /> * [[Dopamine receptor]]<br /> <br /> ===CXCR4 Chemokine Receptor===<br /> * [[CXC chemokine receptor type 4]]<br /> <br /> ===Muscarinic M2 receptor===<br /> * [[3uon]] - human muscarinic M2 receptor, complexed with an antagonist 3-quinuclidinyl-benzilate <br /> <br /> ===Muscarinic M3 receptor===<br /> * [[4daj]] - rat muscarinic M3 receptor, complexed with bronchodilator drug tiotropium <br /> <br /> ===kappa opioid receptor===<br /> * [[4djh]] - human kappa opioid receptor, complexed with antagonist JDTic<br /> <br /> ===mu opioid receptor===<br /> * [[4dkl]] - mouse mu opioid receptor, complexed with an irreversible morphinan antagonist <br /> <br /> ===delta opioid receptor===<br /> * [[4ej4]] - mouse delta opioid receptor, complexed with naltrindole <br /> <br /> ===nociceptin/orphanin FQ receptor===<br /> * [[4ea3]] - human nociceptin/orphanin FQ receptor, complexed with a peptide mimetic antagonist compound 24<br /> <br /> 3kj6<br /> 3ny8<br /> 3ny9<br /> 3nya<br /> 1bl1<br /> 1d6g <br /> 1ddv <br /> 1dep<br /> <br /> 1edw<br /> 1edx<br /> 1ewk<br /> 1ewt<br /> 1ewv<br /> 1f88<br /> 1fdf<br /> 1fjr<br /> 1gzm<br /> 1hll<br /> 1ho9<br /> 1hod<br /> 1hof<br /> 1hzn<br /> ==Nobel Prize Related to the Structures==<br /> [http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2012/ Robert J. Lefkowitz and Brian K. Kobilka share the 2012 Nobel Prize in Chemistry] for work on GPCRs that includes solving the first structures of a ligand-activated GPCR ([[2r4r]], [[2r4s]], & [[2rh1]] in 2007)<ref>PMID: 17962520</ref><ref>PMID: 17962519</ref><ref>PMID: 18033872</ref> and the first activated GPCR in complex with its G protein ([[3sn6]] in 2011)<ref>PMID: 21956322</ref><ref>PMID: 21772288</ref><ref> PMID: 21956331</ref><ref>PMID: 21956322</ref>. A detailed description of the laureates' body of work on this class of receptors with images is [http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2012/popular-chemistryprize2012.pdf here].<br /> <br /> <br /> ==References and Notes==<br /> <references/><br /> <br /> ==See Also==<br /> * [[Nobel Prizes for 3D Molecular Structure]]<br /> * [[Highest impact structures]] of all time<br /> * [[GTP-binding protein| G proteins]]<br /> *[[Rhodopsin]]<br /> * [[GTP-binding protein]]<br /> *[[Pharmaceutical Drugs]]<br /> *[[Membrane proteins]]<br /> *[[Hormone]]<br /> *[[Ligand Binding N-Terminal of Metabotropic Glutamate Receptors]]<br /> <br /> ==Additional Literature==<br /> <ref group="xtra">PMID: xxxx</ref><references group="xtra"/><br /> <br /> ==External Resources==<br /> * [http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2012/ Robert J. Lefkowitz and Brian K. Kobilka share the 2012 Nobel Prize in Chemistry] for work on GPCRs that includes solving the first structures of a ligand-activated GPCR (2007) and the first activated GPCR in complex with its G protein (2011). A detailed description of the laureates' body of work on this class of receptors with images is [http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2012/popular-chemistryprize2012.pdf here].<br /> * The April 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Adrenergic Receptors'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_4 10.2210/rcsb_pdb/mom_2008_4].<br /> *[http://www.gpcr.org/7tm/ GPCRDB: database contains sequences, ligand binding constants and mutations, in addition GPCR multiple sequence alignments and homology models]. Moreover, the site contains useful files where lysozyme and other inserts which are commonly used in the difficult process of [[X-ray crystallography|crystallizing]] these transmembrane structures have been removed from the structures.<br /> * [http://cmpd.scripps.edu/ GPCR Network site] with tracking chart of ongoing structural programs<br /> * [http://www.ssfa-7tmr.de/ssfe/ The GPCR-SSFE Database: A Homology Model Resource for G-Protein Coupled Receptors] <br /> * [http://chembl.blogspot.com/search/label/GPCRs The blog of the Computational Chemical Biology group at the EMBL-EBI] does an excellent job tracking the new GPCR structures as they are emerging.<br /> * [http://www.emeraldbiostructures.com/blog/resources/gpcrs-of-known-structure/ Emerald Biosystems Blog] that features solved structures and on [http://www.emeraldbiostructures.com/blog/entry/gpcr-crystallization-conditions-2 another page] features techniques and amounts needed for crystallization of a number of them.<br /> * [http://www.scripps.edu/news/press/2012/20120712stevens.html A 2012 article from Scripps Research Institute] that covers a lot of history of solving the structures of GPCRs and their importance. <br /> * [http://sbkb.org/update/2012/10/full/sbkb.2012.103.html A 2012 article from the Protein Structure Initiative] on the screening technique to identify stabilizing fusion partners for solving GPCR structure.<br /> * [http://www.nature.com/news/2011/110719/full/475273a.html A 2011 article in Nature entitiled 'Cell Signalling Caught in the Act'] describing the first determination of an activated GPCR — the [[Beta-2 Adrenergic Receptor|β2 adrenergic receptor (β2AR)]] — in a complex with its G protein.<br /> * [http://www.cmbi.ru.nl/tinygrap/ tinyGRAP] GPCR mutant database<br /> * [http://www.gpcr-okb.org/ GPCR-OKB: GPCR Oligomerization Knowledge Base]<br /> * [http://nava.liacs.nl/ GPCR Natural Variants Database (NaVa)]<br /> * [http://athina.biol.uoa.gr/bioinformatics/PRED-GPCR/ The PRED-GPCR server] for GPCR recognition and family classification.<br /> <br /> <br /> [[Category:Topic Page]]<br /> [[Category: G protein-coupled receptor]]<br /> [[Category: G-protein coupled receptor]]<br /> [[Category: G-protein-coupled receptor]]<br /> [[Category: Gpcr]]<br /> [[Category: Membrane protein]]<br /> [[Category: Photoreceptor]]<br /> [[Category: Retinal protein]]</div>

Nikki Hunter https://proteopedia.org/index.php?title=Metabotropic_glutamate_receptor&diff=1867214 Metabotropic glutamate receptor 2013-11-21T19:07:35Z

<p>Nikki Hunter: /* See Also */</p> <hr /> <div>[[Metabotropic glutamate receptor|Metabotropic glutamate receptors]] are [[Glutamate Receptors|glutamate receptors]] that -... They are members of the large class of seven-transmembrane domain receptors, the [[G protein-coupled receptor|G protein-coupled receptors]]. <br /> <Structure load='1isr' size='500' side='right' caption='Structure of the binding domain of the Metabotropic Glutamate Receptor, GluR1, bound to glutamateand gadolinium ions ([[1isr]])' scene=' '/><br /> <br /> Articles in Proteopedia concerning Toll-like Receptors include:<br /> *[[Leucine-rich repeat]]<br /> *[[Membrane proteins]]<br /> <br /><br /> ==3D structures of metabotropic glutamate receptor ==<br /> <br /> ===Metabotropic glutamate receptor 1===<br /> <br /> [[1ewt]], [[1ewv]] - rMGluR1 ligand-binding domain<br /> <br /> [[3ks9]] – hMGluR1 (mutant) + antagonist<br /><br /> [[1isr]], [[1ewk]] – rMGluR1 ligand-binding domain + Glu<br /><br /> [[1iss]] - rMGluR1 ligand-binding domain + antagonist<br /><br /> <br /> ===Metabotropic glutamate receptor 3===<br /> <br /> [[2e4u]] – hMGluR3 ligand-binding domain (mutant) + Glu<br /><br /> [[2e4v]], [[2e4w]], [[2e4x]], [[2e4y]], [[2e4z]] - hMGluR3 ligand-binding domain (mutant) + agonist<br /><br /> <br /> ===Metabotropic glutamate receptor 5===<br /> <br /> [[3lmk]] – hMGluR5 ligand-binding domain (mutant) + positive allosteric modulator + Glu<br /><br /> <br /> ===Metabotropic glutamate receptor 7===<br /> <br /> [[3mq4]] – hMGluR7 ligand-binding domain + antagonist<br /><br /> <br /> <br /> <br /> ==See Also==<br /> [Membrane Channels & Pumps]] <br/><br /> [[Ionotropic_Glutamate_Receptors]]<br/><br /> [[Alzheimer's Disease]]<br/><br /> <br /> * [[Ligand Binding N-Terminal of Metabotropic Glutamate Receptors]]<br /> <br /> [[Category:Topic Page]]<br /> __NOTOC__</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1867213 User:Nikki Hunter/Sandbox 1 2013-11-21T19:05:16Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different [[metabotropic glutamate receptor]]s (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> <br /> <br /> == ABOUT THE MODEL ==<br /> <br /> ----<br /> <br /> <br /> <StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><br /> ==Ligand Binding Action of mGluR N-Terminal== <br /> <scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene><br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu</StructureSection> <br /> <br /> <br /> <br /> == ABOUT THE RECEPTORS ==<br /> <br /> ----<br /> <br /> <br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> <br /> == Resources ==<br /> <br /> ----<br /> <br /> <br /> # Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=Glutamate_receptor_(GluA2)&diff=1867212 Glutamate receptor (GluA2) 2013-11-21T19:02:53Z

<p>Nikki Hunter: /* See Also */</p> <hr /> <div>__NOTOC__<br /> <StructureSection load='3kg2' size='450' side='right' scene='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Default3kg2/1' caption='Ionotropic glutamate receptor tetramer complex with competitive antagonist (PDB code [[3kg2]])' name='main2NDwindow'><br /> <br /> The '''glutamate receptor''' is the ion channel opened by glutamate that keeps neurons in touch by mediating fast cell-to-cell information transfer in the nervous system. Several studies have revealed structures for portions of the glutamate receptor <ref name="r80">PMID: 19461580</ref><ref name="r14">PMID: 19465914</ref><ref name="r22">PMID: 19910922</ref><ref>PMID: 9804426</ref>. Groundbreaking work elucidated the structure of a complete functional, homomeric glutamate receptor<ref name="main">PMID:19946266</ref><ref>PMID: 20010675</ref> and that structure, [[3kg2]], is the subject of this page.<br /> [[Image:3KG2-snapshot-900x900-14724.jpg|left|270px]]<br /> {{clear}} <br /> ==Structure of the Glutamate Receptor (GluA2)==<br /> <br /> ===Overview===<br /> The homomeric rat GluA2 receptor <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Default3kg2/1'>has four subunits</scene> arranged in a 'Y'-shape with the <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Meas3kg2/1'>'top' being about three times the width of the 'bottom'</scene><ref name="main" />. This structure is a functional homotetramer of the AMPA-subtype; native ionotropic glutamate receptors are almost exclusively heterotetramers.&nbsp;{{Link Toggle FancyCartoonHighQualityView}}.<br /> <br /> ===Domains===<br /> The subunits themselves are modular <ref>PMID: 7539962</ref>and the major domains are found in layers in the tetrameric structure.<br /> <br /> *The 'top' layer is composed of the <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Atd_domain/4'>amino-terminal domain(ATD)</scene><br /> ::This <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Atd_gly/2'>extracellular domain is glycosylated</scene>. <br /> *<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Lbd_domain/4'>The ligand-binding domain (LBD)</scene> participates directly in agonist/competitive antagonist binding, affects activation gating, and is the portion that forms the 'middle' layer.<br /> ::<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Lbd_zk1/2'>The competitive antagonist ZK200775 is bound to the LBD</scene> in the structure.<br /> ::The small molecule <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Zk1_zoom/1'>ZK200775, a phosphonate quinoxalinedione AMPA antagonist</scene><ref>PMID: 9724812</ref>, was studied as a treatment for stroke because it had demonstrated neuroprotective efficacy in experimental models of stroke and tolerability in healthy volunteers; however, in a multicenter, double-blind, randomized, placebo-controlled phase II trial, it was found to have significant sedative effects in patients with acute stroke which precludes its further development as a neuroprotective agent<ref>PMID: 16131799</ref>.<br /> *<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Tmd_domain/2'>The transmembrane domain (TMD)</scene> is the portion that forms the membrane-spanning on the 'bottom' of the solved structure.<br /> ::To help give a better idea of how the glutamate receptor is oriented on the cell surface in the membrane lipid bilayer, <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/3kg2opm_mem/11'>a slab representative of hydrophobic core of the lipid bilayer</scene> as calculated by the [http://opm.phar.umich.edu/protein.php?pdbid=3kg2 Orientations of Proteins in Membranes database] (University of Michigan, USA) is shown with the red patch of spheres indicating the boundary of the hydrophobic core closet to the outside of the cell and the dark blue patch of spheres indicating the boundary closest to the inside of the cell.<br /> ::[[Image:Opm_periplasmic_topology.gif]]<br /> * The carboxy-terminal domain that plays a role in both receptor localization and regulation is not seen in the structure but would be below the transmembrane domain as it is cytoplasmic.<br /> <br /> ===Domain swapping between the subunits and symmetry mismatch between the domains===<br /> *Unanticipated is the domain swapping and crossover that occurs between the subunits interactions. In order to discuss the remarkable swapping, it is best to <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Default3kg2letter/4'>designate each subunit with a letter</scene>: <br>&nbsp;&nbsp;&nbsp; '''<span style="color:forestgreen">A</span>'''&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; '''<span style="color:red">B</span>'''&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; '''<span style="color:cornflowerblue">C</span>''' &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; '''D'''<br /> <br /> *Considering each chain, there is crossover as the pairs of subunits seen in the ATD are swapped in the LBD.<br /> ::In the ATD domain - <br /> ::*<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Ab_in_atd/1'>Portions of the A and B subunits pair up</scene>. <br /> ::*And the <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Cd_in_atd/2'>Portions of the C and D subunits form a pair</scene>.<br /> ::*While that is going on, in the ATD there is also inter-pair interactions mediated between <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Abcd_in_atd/2'>subunits B and D</scene>. Note this view really highlights the two-fold symmetry between the A-B and C-D pairs at the level of the ATD.<br /> ::In the LBD domain - <br /> ::*Whereas in the ATD domain A and B paired up, <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Ad_in_lbd/3'>portions of the A and D subunits pair up</scene> in the LBD. <br /> ::*And the <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Bc_in_lbd/1'>Portions of the B and C subunits form a pair</scene>.<br /> ::*While that is going on, in the LBD there is also extensive inter-pair interactions mediated between <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Abcd_in_lbd/6'>subunits A and C</scene>. Note this view highlights the two-fold symmetry between the A-D and B-C pairs at the level of the LBD. <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Abcd_in_lbdside/1'>Looking from the side helps in seeing the inter-pair interactions between A and C</scene>.<br /> :The domain swapping can be observed from the side following the backbone of each chain as well: <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Swap_full_side/1'>A chain</scene>, <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Swap_full_side/2'>B chain</scene>, <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Swap_full_side/3'>C chain</scene>, and <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Swap_full_side/5'>D chain</scene>. And <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Default3kg2letter/4'>all for comparison</scene>.<br /> <br /> *As explored further in [[#Transmembrane domain architecture and the occluded pore|a later section below]] , the <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Tmd_domain_4fold/2'>symmetry is an overall four-fold for the TMD</scene>. Thus, remarkably, the symmetry switches from an overall two-fold symmetry for the ATD and LBD to four-fold for the TMD.<br /> <br /> ===Subunit Non-Equivalence, Transmembrane Domain Architecture and the Occluded Pore===<br /> <br /> ===Subunit non-equivalence===<br /> As a result of the swapping and symmetry mismatch, there is subunit non-equivalence; even though all the chains are the same chemically, there are two distinct conformations of the subunits. This means there are two matching pairs of subunits. <br /> *First pair <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Ac3kg2letter/1'> A is equivalent to C </scene><br /> <br /> *Second pair <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Bd3kg2letter/2'> B is equivalent to D </scene><br /> <br /> * <span style="color:forestgreen">Subunit '''A</span>''' is equivalent to <span style="color:cornflowerblue">Subunit '''C'''</span> (in the small structure window in this section). In the main window, a <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Atocmorph/5' target='main2NDwindow'>morph showing the equivalency of the two subunits by rotating around the axis of their symmetry</scene>.<br /> * <span style="color:red">Subunit '''B</span>''' is equivalent to Subunit '''D''' (in the small structure window in this section).  In the main window, a <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Btodmorph/5' target='main2NDwindow'>morph showing the equivalency of the two subunits by rotating around the axis of their symmetry</scene>.<br /> <br /> However, each of the subunit '''<span style="color:forestgreen">A</span>'''/<span style="color:cornflowerblue">'''C'''</span> group though is distinct from those of the <span style="color:red">'''B</span>'''/'''D''' group. Having established the two equivalent groups we can simplify the discussion of the relationship between the two pairs by focusing solely on comparing <span style="color:forestgreen">Subunit '''A'</span>''' and <span style="color:red">Subunit '''B</span>'''.<br><br /> The domains themselves stay relatively static between the two conformational forms, with the linkers in between and the resulting arrangement changing. This is best illustrated by superposition of the individual domains of <span style="color:forestgreen">Subunit '''A</span>''' and <span style="color:red">Subunit '''B</span>''':<br /> *<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Atdatobsuper/4' target='main2NDwindow'>Superposition of the ATD</scene>.<br /> *<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Lbdatobsuper/2' target='main2NDwindow'>Superposition of the LBD</scene>.<br /> *<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Tmdatobsuper/1' target='main2NDwindow'>Superposition of the TMD</scene>.<br /> <br /> <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Atobmorph/2' target='main2NDwindow'>Subunit A morphing into Subunit B best illustrates how portions, especially the linkers, of the protein change</scene> between the two conformational forms.<br><br /> {{Button Toggle AnimationOnPause}}<br /> :The linkers are key; besides playing roles in domain swapping and resolving the symmetry mismatch, they are also responsible for relaying the modulation signals from the ATD to the other domains and signaling the conformational change of the LBD to control the opening and closing of the pore. Beyond the two conformations seen here though this particular structure ([[3kg2]]) of the receptor does not shed light on the transduction process.<br /> <br /> ===Transmembrane domain architecture and the occluded pore===<br /> *<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Transmemlabeled/1' target='main2NDwindow'>Transmembrane segments M1 to M4 depicted in different colors to show the approximate 4-fold rotational symmetry of the entire ion channel domain.</scene><br /> ::* '''<span style="color:coral">M1</span>'''<br /> ::* '''<span style="color:lightgreen">M2</span>'''<br /> ::* '''<span style="color:violet">M3</span>'''<br /> ::* '''<span style="color:lightskyblue">M4</span>'''<br /> <br /> *The segments shown again, <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Transmem/4' target='main2NDwindow'>this time parallel to the four-fold axis</scene>.<br /> ::There is <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Transmemclosed/1'>no pore visible in the center</scene> consistent with the channel being in a closed state with the antagonist (ZK200775) bound to the LBD.<br /> ::It is <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/M3_closed/3' target='main2NDwindow'>the tight helix crossing of specifically the M3 helices</scene> that occludes the channel. [BE PATIENT as a small surface is generated.]<br /> ::Note <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/M3_closed_top/1' target='main2NDwindow'>the differences between the conformations of the carboxy-termini ('top') of the subunit A/C and B/D M3 segments</scene>. This is in part is why the symmetry is only approximately four-fold and is one of the several intriguing observations in regard to symmetry for this macromolecule. In fact, the location of two-fold symmetry at the ends of M3 is just above the portion that spans the membrane and is close to the last region of the structure that doesn't show four-fold symmetry as abruptly below this point everything is four-fold symmetric.<br /> <br /> *To better observe the contributions of each of the membrane segments to the subunit-subunit interactions, <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Trans_surf/4' target='main2NDwindow'>the transmembrane domains of three subunits are shown in a surface representation with the segments M1-M4 of the fourth subunit shown as green cylinders</scene>. <nowiki>[</nowiki>Note: this scene generates a substantial surface which may take about a minute to calculate. Be patient.<nowiki>]</nowiki><br /> ::Note that the M4 segment associates with the ion-channel core of an adjacent subunit.<br /> :{{Link Toggle FancyCartoonHighQualityView}}.<br /> *The TMD domain of the GluA2 receptor shares structural and sequence similarity with the pore region of the potassium (K+), as hinted at by earlier work<ref name ="pot1">PMID: 7539962</ref><ref name ="pot2">PMID: 7761417</ref><ref name ="pot3">PMID: 9525859</ref>. Here the pore region of ''Streptomyces lividans'' potassium channel ([[1bl8]])<scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Gluvspottmd/4' target='main2NDwindow'> superposed with the TMD domain of GluA2</scene>, specifically the <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Gluvspottmdm3/1' target='main2NDwindow'>inner helix of the K+ channel aligned with the M3 segment</scene>. The <scene name='User:Wayne_Decatur/Sandbox_Glutamate_receptor/Gluvspottmdm1/2' target='main2NDwindow'>M1 segment of GluA2 also overlays well with the outer helix</scene> of the K+ channel even though these portions weren't even included in the calculation of the alignment seen here.<br /> </StructureSection><br /> ==Details of Structure Featured==<br /> [[3kg2]] is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KG2 OCA]. Although it is billed as the first structure of a full-length glutamate receptor, the carboxy-terminal domain is not present in the structure.<br /> <br /> ==Reference for the structure==<br /> <ref group="xtra">PMID:19946266</ref><references group="xtra"/><br /> <br /> ==3D structures of glutamate receptors==<br /> <br /> [[Ionotropic Glutamate Receptors]]<br /> <br /> ==See Also==<br /> <br /> * [[1iiw]] and [[1iit]] and [[1ii5]] – Prokaryotic glutamte receptor (Glur0) Apo structure and with various ligands bound, including glutmate <ref>PMID: 10617203</ref>. This helped cement the notion the glutamate and potassium receptors share structural similarity and possibly evolutionary ancestry <ref name="pot1" /><ref name="pot2" />.<br /> * [[1bl8]] and [[1jq1]] and [[1jq2]] – ''Streptomyces lividans'' KcsA potassium channel<ref name="pot3" /><ref>PMID:11573095</ref>: The M1, M2 and M3 segments of GluA2's ion channel overlap remarkably well with the structurally equivalent portions KcsA. <br /> * [[Molecular Playground/Glutamate Receptor]]<br /> *[[Ligand Binding N-Terminal of Metabotropic Glutamate Receptors]]<br /> <br /> ==References==<br /> {{Reflist}}<br /> <br /> ==Additional Literature and Resources==<br /> * For additional information, see: [[Alzheimer's Disease]]<br /> * For additional information, see: [[Membrane Channels & Pumps]]<br /> * [http://www.nature.com/nature/journal/v462/n7274/covers/ Glutamate Receptor on the cover] of [http://www.nature.com/ Nature]<br /> * [http://en.wikipedia.org/wiki/Glutamate_receptor Glutamate receptor Wikipedia entry]<br /> * [http://www.bristol.ac.uk/synaptic/receptors/#ionotropic Glutamate Receptors page] at the [http://www.bristol.ac.uk/synaptic/ MRC Centre for Synaptic Plasticity at the University of Bristol]<br /> <br /> ''Page started with original page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 16 11:24:54 2009 for [[3kg2]].''<br /> <br /> [[Category: Rattus norvegicus]]<br /> [[Category: Gouaux, E.]]<br /> [[Category: Rosconi, M P.]]<br /> [[Category: Sobolevsky, A I.]]<br /> [[Category: Alternative splicing]]<br /> [[Category: Cell membrane]]<br /> [[Category: Glycoprotein]]<br /> [[Category: Ion channel]]<br /> [[Category: Ion transport]]<br /> [[Category: Membrane]]<br /> [[Category: Membrane protein]]<br /> [[Category: Postsynaptic cell membrane]]<br /> [[Category: Receptor]]<br /> [[Category: Rna editing]]<br /> [[Category: Synapse]]<br /> [[Category: Tetramer]]<br /> [[Category: Transmembrane]]<br /> [[Category: Transport]]<br /> [[Category: Neuron]]<br /> [[Category: Neurotransmitter]]<br /> [[Category: Potassium Channels]]<br /> [[Category: RCSB PDB Molecule of the Month]]<br /> [[Category: Streptomyces lividans]]<br /> [[Category: Cabral, J M.]]<br /> [[Category: Chait, B T.]]<br /> [[Category: Cohen, S L.]]<br /> [[Category: Doyle, D A.]]<br /> [[Category: Gulbis, J M.]]<br /> [[Category: Kuo, A.]]<br /> [[Category: Mackinnon, R.]]<br /> [[Category: Pfuetzner, R A.]]<br /> [[Category: Integral membrane protein]]<br /> [[Category: Potassium channel]]<br /> [[Category:Topic Page]]</div>

Nikki Hunter https://proteopedia.org/index.php?title=Ligand_Binding_N-Terminal_of_Metabotropic_Glutamate_Receptors&diff=1867211 Ligand Binding N-Terminal of Metabotropic Glutamate Receptors 2013-11-21T18:58:13Z

<p>Nikki Hunter: New page: == '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' == This page showcases a homology model, created from the N-terminal structures of two different [[metabotropic glut...</p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different [[metabotropic glutamate receptor]]s (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> <br /> <br /> == ABOUT THE MODEL ==<br /> <br /> <br /> <StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><br /> ==Ligand Binding Action of mGluR N-Terminal== <br /> <scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene><br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu</StructureSection> <br /> <br /> <br /> <br /> == ABOUT THE RECEPTORS ==<br /> <br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> == PLACE IN DRUG DISCOVERY ==<br /> <br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> == Resources ==<br /> <br /> ----<br /> <br /> # Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1864556 User:Nikki Hunter/Sandbox 1 2013-11-14T16:52:04Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different [[metabotropic glutamate receptors]] (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> <br /> <br /> == ABOUT THE MODEL ==<br /> <br /> ----<br /> <br /> <br /> <StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><br /> ==Ligand Binding Action of mGluR N-Terminal== <br /> <scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene><br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu</StructureSection> <br /> <br /> <br /> <br /> == ABOUT THE RECEPTORS ==<br /> <br /> ----<br /> <br /> <br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> <br /> == Resources ==<br /> <br /> ----<br /> <br /> <br /> # Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1864555 User:Nikki Hunter/Sandbox 1 2013-11-14T16:50:13Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different [[metabotropic glutamate receptors]] (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> <br /> <br /> == ABOUT THE MODEL ==<br /> <br /> ----<br /> <br /> <br /> <StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene><br /> <br /> ==Ligand Binding Action of mGluR N-Terminal== <br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu</StructureSection> <br /> <br /> <br /> <br /> == ABOUT THE RECEPTORS ==<br /> <br /> ----<br /> <br /> <br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> <br /> == Resources ==<br /> <br /> ----<br /> <br /> <br /> # Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1864554 User:Nikki Hunter/Sandbox 1 2013-11-14T16:48:04Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different [[metabotropic glutamate receptors]] (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> <br /> <br /> == ABOUT THE MODEL ==<br /> <br /> ----<br /> <br /> <br /> ==Ligand Binding Action of mGluR N-Terminal==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene><br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu</StructureSection> <br /> <br /> <br /> <br /> == ABOUT THE RECEPTORS ==<br /> <br /> ----<br /> <br /> <br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> <br /> == Resources ==<br /> <br /> ----<br /> <br /> <br /> # Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1864552 User:Nikki Hunter/Sandbox 1 2013-11-14T16:45:22Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different [[metabotropic glutamate receptors]] (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> <br /> <br /> == ABOUT THE MODEL ==<br /> <br /> ----<br /> <br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> <br /> =='''Ligand Binding Action of mGluR N-Terminal'''==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene></StructureSection> <br /> <br /> <br /> <br /> == ABOUT THE RECEPTORS ==<br /> <br /> ----<br /> <br /> <br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> <br /> == Resources ==<br /> <br /> ----<br /> <br /> <br /> # Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1864549 User:Nikki Hunter/Sandbox 1 2013-11-14T16:39:32Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different [[metabotropic glutamate receptors]] (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> ----<br /> <br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> <br /> =='''Ligand Binding Action of mGluR N-Terminal'''==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene></StructureSection><br /> ----<br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''Resources''' :<br /> <br /> # Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1864546 User:Nikki Hunter/Sandbox 1 2013-11-14T16:32:16Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different mGlu Receptors (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> ----<br /> <br /> <br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> ----<br /> <br /> =='''Ligand Binding Action of mGluR N-Terminal'''==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene></StructureSection><br /> ----<br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''Resources''' :<br /> <br /> # Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1864544 User:Nikki Hunter/Sandbox 1 2013-11-14T16:30:52Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different mGlu Receptors (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> ----<br /> <br /> <br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> ----<br /> <br /> =='''Ligand Binding Action of mGluR N-Terminal'''==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene></StructureSection><br /> ----<br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''Resources''' :<br /> <br /> # Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> <br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> <br /> # Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1864543 User:Nikki Hunter/Sandbox 1 2013-11-14T16:28:06Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different mGlu Receptors (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> ----<br /> <br /> <br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [http://molmovdb.org/ Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> ----<br /> <br /> =='''Ligand Binding Action of mGluR N-Terminal'''==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene></StructureSection><br /> ----<br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''Resources''' :<br /> <br /> 1. Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of<br /> Pharmacology (2009) 156:869-884. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697712/]<br /> <br /> 2. Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami<br /> H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created<br /> using JMOL. [http://www.rcsb.org/pdb/explore/explore.do?structureId=1ewk]<br /> <br /> 3. Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of<br /> the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL. [http://www.rcsb.org/pdb/explore.do?structureId=2e4y]</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1862053 User:Nikki Hunter/Sandbox 1 2013-11-12T17:55:53Z

<p>Nikki Hunter: /* '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' */</p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different mGlu Receptors (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> ----<br /> <br /> <br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> ----<br /> <br /> ==Ligand Binding Action of mGluR N-Terminal==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene></StructureSection><br /> ----<br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''Resources''' :<br /> <br /> Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884.<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1862051 User:Nikki Hunter/Sandbox 1 2013-11-12T17:50:34Z

<p>Nikki Hunter: /* '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' */</p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> <br /> This page showcases a homology model, created from the N-terminal structures of two different mGlu Receptors (2e4y and 2ewk). This model is used to animate the action that occurs when there is interaction with a ligand inside the ligand binding pocket of the domain. <br /> <br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the [Yale Morph Server]. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> ----<br /> <br /> ==Ligand Binding Action of mGluR N-Terminal==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene></StructureSection><br /> ----<br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''Resources''' :<br /> <br /> Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884.<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1862050 User:Nikki Hunter/Sandbox 1 2013-11-12T17:43:11Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the Yale Morph Server. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> ----<br /> <br /> ==Ligand Binding Action of mGluR N-Terminal==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene></StructureSection><br /> ----<br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''Resources''' :<br /> <br /> Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884.<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1862048 User:Nikki Hunter/Sandbox 1 2013-11-12T17:40:08Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the Yale Morph Server. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <br /> <br /> <br /> ----<br /> <br /> ==Ligand Binding Action of mGluR N-Terminal==<StructureSection load='All.pdb' size='500' side='right' caption='mGluR homology model representing the N-terminal of the receptor which undergoes conformational change upon ligand interaction' scene=''><scene name='56/568036/Venusft/3'>CLICK HERE to animate the structure and view the action that occurs during ligand binding</scene></StructureSection><br /> ----<br /> <br /> <br /> '''Resources''' :<br /> <br /> Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884.<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1862038 User:Nikki Hunter/Sandbox 1 2013-11-12T16:44:48Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the Yale Morph Server. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> ----<br /> <br /> <br /> '''Resources''' :<br /> <br /> Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884.<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL<br /> <br /> <br /> ----<br /> <scene name='56/568036/Venusft/1'>Ligand Binding Action N-Terminal of mGluR</scene></div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter/Sandbox_1&diff=1862035 User:Nikki Hunter/Sandbox 1 2013-11-12T16:27:50Z

<p>Nikki Hunter: New page: == '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' == '''ABOUT THE MODEL''': This animation represents the Venus flytrap-type-of-action that occurs at the extracellula...</p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the Yale Morph Server. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> ----<br /> <br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> ----<br /> <br /> <br /> '''Resources''' :<br /> <br /> Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884.<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL<br /> <br /> <br /> ----</div>

Nikki Hunter https://proteopedia.org/index.php?title=User:Nikki_Hunter&diff=1862034 User:Nikki Hunter 2013-11-12T16:27:09Z

<p>Nikki Hunter: </p> <hr /> <div>* Full Real Name: Nikki Hunter<br /> <br /> * Position:student<br /> <br /> * Institution (NO ABBREVIATIONS): South University School of Pharmacy<br /> <br /> * City, State/Province, Country: Savannah, Georgia, USA<br /> <br /> * Field of Expertise or Study: Pharmacy<br /> *[[User:Nikki Hunter/Sandbox 1]]</div>

Nikki Hunter https://proteopedia.org/index.php?title=NIkkihunter/Sandbox1&diff=1861934 NIkkihunter/Sandbox1 2013-11-11T19:35:58Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the Yale Morph Server. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> '''Resources''' :<br /> <br /> Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884.<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL<br /> <br /> <br /> <br /> <StructureSection load='<scene name='56/568006/Vfltrap/1'>' size='350' side='right' caption='Conformational change in mGluR N-Terminal during ligand binding =''></div>

Nikki Hunter https://proteopedia.org/index.php?title=NIkkihunter/Sandbox1&diff=1861933 NIkkihunter/Sandbox1 2013-11-11T19:28:08Z

<p>Nikki Hunter: </p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the Yale Morph Server. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> '''Resources''' :<br /> <br /> Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884.<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL<br /> <br /> <br /> <br /> <StructureSection load='<scene name='56/568006/Vflytrap_action/4'>TextToBeDisplayed</scene>' size='350' side='right' caption='Conformational change in mGluR N-Terminal during ligand binding =''></div>

Nikki Hunter https://proteopedia.org/index.php?title=File:All.pdb&diff=1861932 File:All.pdb 2013-11-11T19:12:57Z

<p>Nikki Hunter: uploaded a new version of "Image:All.pdb"</p> <hr /> <div>morph caspase-3 from unbound to bound</div>

Nikki Hunter https://proteopedia.org/index.php?title=File:Flytrap.spt&diff=1861929 File:Flytrap.spt 2013-11-11T19:05:15Z

<p>Nikki Hunter: uploaded a new version of "Image:Flytrap.spt"</p> <hr /> <div>== Summary ==<br /> Venus Flytrap-like action of N-terminal domain of mGlu receptors<br /> == Licensing ==<br /> {{PD-self}}</div>

Nikki Hunter https://proteopedia.org/index.php?title=NIkkihunter/Sandbox1&diff=1861928 NIkkihunter/Sandbox1 2013-11-11T18:59:12Z

<p>Nikki Hunter: Ligand Binding N-Terminal of Metabotropic Glutamate Receptors</p> <hr /> <div>== '''Ligand Binding N-Terminal of Metabotropic Glutamate Receptors''' ==<br /> '''ABOUT THE MODEL''':<br /> <br /> This animation represents the Venus flytrap-type-of-action that occurs at the extracellular N-terminal domain, when a binding ligand causes conformational change.<br /> <br /> To create this model, two crystallized metabotropic glutamate receptors, in different conformations, from the protein data bank, were homogenized using the Yale Morph Server. <br /> <br /> 1. [[2e4y]] : hMGluR3 ligand binding domain (mutant) + agonist <br /> <br /> 2. [[2ewk]] : rMGluR1 ligand binding domain + Glu<br /> <br /> <br /> <br /> '''ABOUT THE RECEPTORS''':<br /> <br /> Metabotropic Glutamate Receptors are members of the large class of 7-transmembrane domain receptors, G-Protein Coupled Receptors (GPCR) and the subclass, Family C.<br /> <br /> Family C GPCRs have a large extracellular N-terminal (as shown in the animation) that bind to the uninhibited ligand, resulting in the conformational change of the extracellular portion of the receptor. There have been several different ligands identified that have affinity to these sites. <br /> <br /> The metabotropic glutamate receptors (mGluRs) play a large role in the alteration of excitatory synaptic transmission in the central nervous system. In short, they affect the activity of other receptors, such as NMDA receptors.<br /> <br /> <br /> [[Image:mgluSM.png]]<br /> <br /> <br /> '''PLACE IN DRUG DISCOVERY''':<br /> <br /> The mGluR3 receptor has been associated with psychological disorders such as bipolar affective disorder and schizophrenia. The GRM3 gene (the gene encoding for mGluR3) is a likely cause of genetic predisposition to a genetic subtype of bipolar affective disorder making it an area of interest for medicinal research regarding patient specific, customizable, psychiatric medication.<br /> <br /> Studies regarding mGluRs suggest they may have some potential in the area of drug research regarding: pain, motor function, memory, autism, neuroimaging and more. Some manipulations suggest it could be an area of interest regarding neuroprotective agents. <br /> <br /> Studies with mutant mice have shown mutations in mGluR1 to have possible involvement with certain types of cancer, specifically melanomas. <br /> <br /> <br /> <StructureSection load='flytrap.spt' size='350' side='right' caption='Conformational change in mGluR N-Terminal during ligand binding =''><br /> Anything in this section will appear adjacent to the 3D structure and will be scrollable.<br /> <br /> <br /> <br /> '''Resources''' :<br /> <br /> Wellendorph D, Brauner-Osborne H, “Review: Molecular Basis for Amino Acid Sensing by Family C G-Protein-Coupled Receptors.” British Journal of Pharmacology (2009) 156:869-884.<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 1EWK (Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K, “Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.” (2000) Nature 407: 971-977) created using JMOL<br /> <br /> Image from the RCSB PDB (www.pdb.org) of PDB ID of 2E4Y (Muto T, Tsuchiya D, Morikawa K, Jingami H, “Structures of the Extracellular Region of the Group II/ III Metabotropicgltamate Receptors.” (2007) Proc.Natl.Acad.Sci.USA 104:3759-3764) created using JMOL</div>

Nikki Hunter https://proteopedia.org/index.php?title=File:MgluSM.png&diff=1861927 File:MgluSM.png 2013-11-11T18:43:46Z

<p>Nikki Hunter: mglu family tree</p> <hr /> <div>mglu family tree</div>

Nikki Hunter https://proteopedia.org/index.php?title=File:Flytrap.spt&diff=1861925 File:Flytrap.spt 2013-11-11T18:29:44Z

<p>Nikki Hunter: Venus Flytrap-like action of N-terminal domain of mGlu receptors</p> <hr /> <div>== Summary ==<br /> Venus Flytrap-like action of N-terminal domain of mGlu receptors<br /> == Licensing ==<br /> {{PD-self}}</div>

Nikki Hunter