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| | <StructureSection load='6kk1' size='340' side='right'caption='[[6kk1]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='6kk1' size='340' side='right'caption='[[6kk1]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6kk1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KK1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KK1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6kk1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KK1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KK1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=97Y:N-{4-[(R)-(3,3-DIMETHYLCYCLOBUTYL)({6-[4-(TRIFLUOROMETHYL)-1H-IMIDAZOL-1-YL]PYRIDIN-3-YL}AMINO)METHYL]BENZENE-1-CARBONYL}-BETA-ALANINE'>97Y</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]] 2.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vew|5vew]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=97Y:N-{4-[(R)-(3,3-DIMETHYLCYCLOBUTYL)({6-[4-(TRIFLUOROMETHYL)-1H-IMIDAZOL-1-YL]PYRIDIN-3-YL}AMINO)METHYL]BENZENE-1-CARBONYL}-BETA-ALANINE'>97Y</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLP1R ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6kk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kk1 OCA], [https://pdbe.org/6kk1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kk1 RCSB], [https://www.ebi.ac.uk/pdbsum/6kk1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kk1 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=6kk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kk1 OCA], [http://pdbe.org/6kk1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kk1 RCSB], [http://www.ebi.ac.uk/pdbsum/6kk1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kk1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLP1R_HUMAN GLP1R_HUMAN]] This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. | + | [https://www.uniprot.org/uniprot/GLP1R_HUMAN GLP1R_HUMAN] This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.[https://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.<ref>PMID:22389108</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6kk1" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6kk1" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glucagon-like peptide receptor 3D structures|Glucagon-like peptide receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Escherichia virus T4]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Song, G]] | + | [[Category: Song G]] |
| - | [[Category: Allosteric modulator]]
| + | |
| - | [[Category: Diabetes]]
| + | |
| - | [[Category: Gpcr]]
| + | |
| - | [[Category: Seven-transmembrane]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
GLP1R_HUMAN This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[1]
Publication Abstract from PubMed
The class B family of G-protein-coupled receptors (GPCRs) has long been a paradigm for peptide hormone recognition and signal transduction. One class B GPCR, the glucagon-like peptide-1 receptor (GLP-1R), has been considered as an anti-diabetes drug target and there are several peptidic drugs available for the treatment of this overwhelming disease. The previously determined structures of inactive GLP-1R in complex with two negative allosteric modulators include ten thermal-stabilizing mutations that were selected from a total of 98 designed mutations. Here we systematically summarize all 98 mutations we have tested and the results suggest that the mutagenesis strategy that strengthens inter-helical hydro-phobic interactions shows the highest success rate. We further investigate four back mutations by thermal-shift assay, crystallization and molecular dynamic simulations, and conclude that mutation I196(2.66b)F increases thermal stability intrinsically and that mutation S271(4.47b)A decreases crystal packing entropy extrinsically, while mutations S193(2.63b)C and M233(3.36b)C may be dispensable since these two cysteines are not di-sulfide-linked. Our results indicate intrinsic connections between different regions of GPCR transmembrane helices and the current data suggest a general mutagenesis principle for structural determination of GPCRs and other membrane proteins.
Mutagenesis facilitated crystallization of GLP-1R.,Xu Y, Wang Y, Wang Y, Liu K, Peng Y, Yao D, Tao H, Liu H, Song G IUCrJ. 2019 Oct 17;6(Pt 6):996-1006. doi: 10.1107/S2052252519013496. eCollection , 2019 Nov 1. PMID:31709055[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. Protein determinants of phage T4 lysis inhibition. Protein Sci. 2012 Apr;21(4):571-82. doi: 10.1002/pro.2042. Epub 2012 Mar 2. PMID:22389108 doi:http://dx.doi.org/10.1002/pro.2042
- ↑ Xu Y, Wang Y, Wang Y, Liu K, Peng Y, Yao D, Tao H, Liu H, Song G. Mutagenesis facilitated crystallization of GLP-1R. IUCrJ. 2019 Oct 17;6(Pt 6):996-1006. doi: 10.1107/S2052252519013496. eCollection , 2019 Nov 1. PMID:31709055 doi:http://dx.doi.org/10.1107/S2052252519013496
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