7fee

From Proteopedia

(Difference between revisions)

Revision as of 17:14, 29 November 2023

Crystal Structure of protein l

Structural highlights

7fee is a 1 chain structure with sequence from Homo sapiens and Pyrococcus abyssi GE5. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q9V2J8_PYRAB CNR1_HUMAN Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.^[1]

Publication Abstract from PubMed

Given the promising clinical value of allosteric modulators of G protein-coupled-receptors (GPCRs), mechanistic understanding of how these modulators alter GPCR function is of significance. Here, we report the crystallographic and cryo-electron microscopy structures of the cannabinoid receptor CB1 bound to the positive allosteric modulator (PAM) ZCZ011. These structures show that ZCZ011 binds to an extrahelical site in the transmembrane 2 (TM2)-TM3-TM4 surface. Through (un)biased molecular dynamics simulations and mutagenesis experiments, we show that TM2 rearrangement is critical for the propagation of allosteric signals. ZCZ011 exerts a PAM effect by promoting TM2 rearrangement in favor of receptor activation and increasing the population of receptors that adopt an active conformation. In contrast, ORG27569, a negative allosteric modulator (NAM) of CB1, also binds to the TM2-TM3-TM4 surface and exerts a NAM effect by impeding the TM2 rearrangement. Our findings fill a gap in the understanding of CB1 allosteric regulation and could guide the rational design of CB1 allosteric modulators.

Molecular mechanism of allosteric modulation for the cannabinoid receptor CB1.,Yang X, Wang X, Xu Z, Wu C, Zhou Y, Wang Y, Lin G, Li K, Wu M, Xia A, Liu J, Cheng L, Zou J, Yan W, Shao Z, Yang S Nat Chem Biol. 2022 May 30. pii: 10.1038/s41589-022-01038-y. doi:, 10.1038/s41589-022-01038-y. PMID:35637350^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ryberg E, Vu HK, Larsson N, Groblewski T, Hjorth S, Elebring T, Sjogren S, Greasley PJ. Identification and characterisation of a novel splice variant of the human CB1 receptor. FEBS Lett. 2005 Jan 3;579(1):259-64. PMID:15620723 doi:http://dx.doi.org/10.1016/j.febslet.2004.11.085
↑ Yang X, Wang X, Xu Z, Wu C, Zhou Y, Wang Y, Lin G, Li K, Wu M, Xia A, Liu J, Cheng L, Zou J, Yan W, Shao Z, Yang S. Molecular mechanism of allosteric modulation for the cannabinoid receptor CB1. Nat Chem Biol. 2022 May 30. pii: 10.1038/s41589-022-01038-y. doi:, 10.1038/s41589-022-01038-y. PMID:35637350 doi:http://dx.doi.org/10.1038/s41589-022-01038-y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7fee"

@@ Line 3: / Line 3: @@
 <StructureSection load='7fee' size='340' side='right'caption='[[7fee]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7fee]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FEE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FEE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7fee]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Pyrococcus_abyssi_GE5 Pyrococcus abyssi GE5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FEE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FEE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7IC:6-methyl-3-[(1S)-2-nitro-1-thiophen-2-yl-ethyl]-2-phenyl-1H-indole'>7IC</scene>, <scene name='pdbligand=9GF:2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol'>9GF</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7IC:6-methyl-3-[(1S)-2-nitro-1-thiophen-2-yl-ethyl]-2-phenyl-1H-indole'>7IC</scene>, <scene name='pdbligand=9GF:2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol'>9GF</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7fee FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fee OCA], [https://pdbe.org/7fee PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fee RCSB], [https://www.ebi.ac.uk/pdbsum/7fee PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fee ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/CNR1_HUMAN CNR1_HUMAN]] Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.<ref>PMID:15620723</ref>
+[https://www.uniprot.org/uniprot/Q9V2J8_PYRAB Q9V2J8_PYRAB] [https://www.uniprot.org/uniprot/CNR1_HUMAN CNR1_HUMAN] Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.<ref>PMID:15620723</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Shao, Z]]
+[[Category: Pyrococcus abyssi GE5]]
-[[Category: Wang, X]]
+[[Category: Shao Z]]
-[[Category: Zhao, C]]
+[[Category: Wang X]]
-[[Category: Gpcr]]
+[[Category: Zhao C]]
-[[Category: Membrane protein]]
-[[Category: Signal protein]]

7fee

From Proteopedia

Revision as of 17:14, 29 November 2023

Crystal Structure of protein l

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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