6ps7: Difference between revisions

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<StructureSection load='6ps7' size='340' side='right'caption='[[6ps7]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
<StructureSection load='6ps7' size='340' side='right'caption='[[6ps7]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6ps7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PS7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PS7 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6ps7]] is a 1 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=6PS7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PS7 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLB:(2S)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLB</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=ZMA:4-{2-[(7-AMINO-2-FURAN-2-YL[1,2,4]TRIAZOLO[1,5-A][1,3,5]TRIAZIN-5-YL)AMINO]ETHYL}PHENOL'>ZMA</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLB:(2S)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLB</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=ZMA:4-{2-[(7-AMINO-2-FURAN-2-YL[1,2,4]TRIAZOLO[1,5-A][1,3,5]TRIAZIN-5-YL)AMINO]ETHYL}PHENOL'>ZMA</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADORA2A, ADORA2 ([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=6ps7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ps7 OCA], [http://pdbe.org/6ps7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ps7 RCSB], [http://www.ebi.ac.uk/pdbsum/6ps7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ps7 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=6ps7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ps7 OCA], [http://pdbe.org/6ps7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ps7 RCSB], [http://www.ebi.ac.uk/pdbsum/6ps7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ps7 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/AA2AR_HUMAN AA2AR_HUMAN]] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.  
[[http://www.uniprot.org/uniprot/AA2AR_HUMAN AA2AR_HUMAN]] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Rational structure-based drug design (SBDD) relies on the availability of a large number of co-crystal structures to map the ligand-binding pocket of the target protein and use this information for lead-compound optimization via an iterative process. While SBDD has proven successful for many drug-discovery projects, its application to G protein-coupled receptors (GPCRs) has been limited owing to extreme difficulties with their crystallization. Here, a method is presented for the rapid determination of multiple co-crystal structures for a target GPCR in complex with various ligands, taking advantage of the serial femtosecond crystallography approach, which obviates the need for large crystals and requires only submilligram quantities of purified protein. The method was applied to the human beta2-adrenergic receptor, resulting in eight room-temperature co-crystal structures with six different ligands, including previously unreported structures with carvedilol and propranolol. The generality of the proposed method was tested with three other receptors. This approach has the potential to enable SBDD for GPCRs and other difficult-to-crystallize membrane proteins.
Toward G protein-coupled receptor structure-based drug design using X-ray lasers.,Ishchenko A, Stauch B, Han GW, Batyuk A, Shiriaeva A, Li C, Zatsepin N, Weierstall U, Liu W, Nango E, Nakane T, Tanaka R, Tono K, Joti Y, Iwata S, Moraes I, Gati C, Cherezov V IUCrJ. 2019 Oct 24;6(Pt 6):1106-1119. doi: 10.1107/S2052252519013137. eCollection, 2019 Nov 1. PMID:31709066<ref>PMID:31709066</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ps7" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bacillus coli migula 1895]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Batyuk, A]]
[[Category: Batyuk, A]]

Revision as of 16:08, 25 December 2019

XFEL A2aR structure by ligand exchange from LUF5843 to ZM241385.XFEL A2aR structure by ligand exchange from LUF5843 to ZM241385.

Structural highlights

6ps7 is a 1 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , , ,
Gene:ADORA2A, ADORA2 ("Bacillus coli" Migula 1895)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[AA2AR_HUMAN] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.

Publication Abstract from PubMed

Rational structure-based drug design (SBDD) relies on the availability of a large number of co-crystal structures to map the ligand-binding pocket of the target protein and use this information for lead-compound optimization via an iterative process. While SBDD has proven successful for many drug-discovery projects, its application to G protein-coupled receptors (GPCRs) has been limited owing to extreme difficulties with their crystallization. Here, a method is presented for the rapid determination of multiple co-crystal structures for a target GPCR in complex with various ligands, taking advantage of the serial femtosecond crystallography approach, which obviates the need for large crystals and requires only submilligram quantities of purified protein. The method was applied to the human beta2-adrenergic receptor, resulting in eight room-temperature co-crystal structures with six different ligands, including previously unreported structures with carvedilol and propranolol. The generality of the proposed method was tested with three other receptors. This approach has the potential to enable SBDD for GPCRs and other difficult-to-crystallize membrane proteins.

Toward G protein-coupled receptor structure-based drug design using X-ray lasers.,Ishchenko A, Stauch B, Han GW, Batyuk A, Shiriaeva A, Li C, Zatsepin N, Weierstall U, Liu W, Nango E, Nakane T, Tanaka R, Tono K, Joti Y, Iwata S, Moraes I, Gati C, Cherezov V IUCrJ. 2019 Oct 24;6(Pt 6):1106-1119. doi: 10.1107/S2052252519013137. eCollection, 2019 Nov 1. PMID:31709066[1]

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

References

  1. ↑ Ishchenko A, Stauch B, Han GW, Batyuk A, Shiriaeva A, Li C, Zatsepin N, Weierstall U, Liu W, Nango E, Nakane T, Tanaka R, Tono K, Joti Y, Iwata S, Moraes I, Gati C, Cherezov V. Toward G protein-coupled receptor structure-based drug design using X-ray lasers. IUCrJ. 2019 Oct 24;6(Pt 6):1106-1119. doi: 10.1107/S2052252519013137. eCollection, 2019 Nov 1. PMID:31709066 doi:http://dx.doi.org/10.1107/S2052252519013137

6ps7, resolution 1.85Å

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