6me8

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<StructureSection load='6me8' size='340' side='right'caption='[[6me8]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
<StructureSection load='6me8' size='340' side='right'caption='[[6me8]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6me8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ME8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ME8 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6me8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ME8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ME8 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JEY:N-[2-(5-methoxy-2-phenyl-1H-indol-3-yl)ethyl]acetamide'>JEY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JEY:N-[2-(5-methoxy-2-phenyl-1H-indol-3-yl)ethyl]acetamide'>JEY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MTNR1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6me8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6me8 OCA], [http://pdbe.org/6me8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6me8 RCSB], [http://www.ebi.ac.uk/pdbsum/6me8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6me8 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6me8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6me8 OCA], [http://pdbe.org/6me8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6me8 RCSB], [http://www.ebi.ac.uk/pdbsum/6me8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6me8 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX]] Electron-transport protein of unknown function.
[[http://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX]] Electron-transport protein of unknown function.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The human MT1 and MT2 melatonin receptors(1,2) are G-protein-coupled receptors (GPCRs) that help to regulate circadian rhythm and sleep patterns(3). Drug development efforts have targeted both receptors for the treatment of insomnia, circadian rhythm and mood disorders, and cancer(3), and MT2 has also been implicated in type 2 diabetes(4,5). Here we report X-ray free electron laser (XFEL) structures of the human MT2 receptor in complex with the agonists 2-phenylmelatonin (2-PMT) and ramelteon(6) at resolutions of 2.8 A and 3.3 A, respectively, along with two structures of function-related mutants: H208(5.46)A (superscripts represent the Ballesteros-Weinstein residue numbering nomenclature(7)) and N86(2.50)D, obtained in complex with 2-PMT. Comparison of the structures of MT2 with a published structure(8) of MT1 reveals that, despite conservation of the orthosteric ligand-binding site residues, there are notable conformational variations as well as differences in [(3)H]melatonin dissociation kinetics that provide insights into the selectivity between melatonin receptor subtypes. A membrane-buried lateral ligand entry channel is observed in both MT1 and MT2, but in addition the MT2 structures reveal a narrow opening towards the solvent in the extracellular part of the receptor. We provide functional and kinetic data that support a prominent role for intramembrane ligand entry in both receptors, and suggest that there might also be an extracellular entry path in MT2. Our findings contribute to a molecular understanding of melatonin receptor subtype selectivity and ligand access modes, which are essential for the design of highly selective melatonin tool compounds and therapeutic agents.
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XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity.,Johansson LC, Stauch B, McCorvy JD, Han GW, Patel N, Huang XP, Batyuk A, Gati C, Slocum ST, Li C, Grandner JM, Hao S, Olsen RHJ, Tribo AR, Zaare S, Zhu L, Zatsepin NA, Weierstall U, Yous S, Stevens RC, Liu W, Roth BL, Katritch V, Cherezov V Nature. 2019 May;569(7755):289-292. doi: 10.1038/s41586-019-1144-0. Epub 2019 Apr, 24. PMID:31019305<ref>PMID:31019305</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6me8" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bacillus coli migula 1895]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Batyuk, A]]
[[Category: Batyuk, A]]

Revision as of 13:39, 10 May 2019

XFEL crystal structure of human melatonin receptor MT2 (N86D) in complex with 2-phenylmelatonin

PDB ID 6me8

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