5zbh
From Proteopedia
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<StructureSection load='5zbh' size='340' side='right' caption='[[5zbh]], [[Resolution|resolution]] 3.00Å' scene=''> | <StructureSection load='5zbh' size='340' side='right' caption='[[5zbh]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5zbh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZBH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zbh]] is a 1 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=5ZBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZBH FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9AF:dimethyl+4-{3-[({3-[4-(3-methoxyphenyl)piperidin-1-yl]propyl}carbamoyl)amino]phenyl}-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate'>9AF</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9AF:dimethyl+4-{3-[({3-[4-(3-methoxyphenyl)piperidin-1-yl]propyl}carbamoyl)amino]phenyl}-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate'>9AF</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NPY1R, NPYR, NPYY1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </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=5zbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zbh OCA], [http://pdbe.org/5zbh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zbh RCSB], [http://www.ebi.ac.uk/pdbsum/5zbh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zbh 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=5zbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zbh OCA], [http://pdbe.org/5zbh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zbh RCSB], [http://www.ebi.ac.uk/pdbsum/5zbh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zbh ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/NPY1R_HUMAN NPY1R_HUMAN]] Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY > [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY > NPY (2-36) > [Ile-31, Gln-34] PP and PYY (3-36) > PP > NPY free acid. | [[http://www.uniprot.org/uniprot/NPY1R_HUMAN NPY1R_HUMAN]] Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY > [Pro-34] PYY, PYY and [Leu-31, Pro-34] NPY > NPY (2-36) > [Ile-31, Gln-34] PP and PYY (3-36) > PP > NPY free acid. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor superfamily and have important roles in food intake, anxiety and cancer biology (1,2) . The NPY-Y receptor system has emerged as one of the most complex networks with three peptide ligands (NPY, peptide YY and pancreatic polypeptide) binding to four receptors in most mammals, namely the Y1, Y2, Y4 and Y5 receptors, with different affinity and selectivity (3) . NPY is the most powerful stimulant of food intake and this effect is primarily mediated by the Y1 receptor (Y1R) (4) . A number of peptides and small-molecule compounds have been characterized as Y1R antagonists and have shown clinical potential in the treatment of obesity (4) , tumour (1) and bone loss (5) . However, their clinical usage has been hampered by low potency and selectivity, poor brain penetration ability or lack of oral bioavailability (6) . Here we report crystal structures of the human Y1R bound to the two selective antagonists UR-MK299 and BMS-193885 at 2.7 and 3.0 A resolution, respectively. The structures combined with mutagenesis studies reveal the binding modes of Y1R to several structurally diverse antagonists and the determinants of ligand selectivity. The Y1R structure and molecular docking of the endogenous agonist NPY, together with nuclear magnetic resonance, photo-crosslinking and functional studies, provide insights into the binding behaviour of the agonist and for the first time, to our knowledge, determine the interaction of its N terminus with the receptor. These insights into Y1R can enable structure-based drug discovery that targets NPY receptors. | ||
| + | |||
| + | Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor.,Yang Z, Han S, Keller M, Kaiser A, Bender BJ, Bosse M, Burkert K, Kogler LM, Wifling D, Bernhardt G, Plank N, Littmann T, Schmidt P, Yi C, Li B, Ye S, Zhang R, Xu B, Larhammar D, Stevens RC, Huster D, Meiler J, Zhao Q, Beck-Sickinger AG, Buschauer A, Wu B Nature. 2018 Apr;556(7702):520-524. doi: 10.1038/s41586-018-0046-x. Epub 2018 Apr, 18. PMID:29670288<ref>PMID:29670288</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5zbh" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Lysozyme]] | [[Category: Lysozyme]] | ||
[[Category: Han, S]] | [[Category: Han, S]] | ||
Revision as of 08:28, 2 May 2018
The Crystal Structure of Human Neuropeptide Y Y1 Receptor with BMS-193885
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