View source for 5zbq


==The Crystal Structure of human neuropeptide Y Y1 receptor with UR-MK299==
<StructureSection load='5zbq' size='340' side='right'caption='[[5zbq]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zbq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacteria_phage_RB55 Enterobacteria phage RB55] 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=5ZBQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZBQ FirstGlance]. <br>
</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=9AO:N~2~-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-N~5~-(N-{[2-(propanoylamino)ethyl]carbamoyl}carbamimidoyl)-D-ornithinamide'>9AO</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=5zbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zbq OCA], [https://pdbe.org/5zbq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zbq RCSB], [https://www.ebi.ac.uk/pdbsum/5zbq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zbq ProSAT]</span></td></tr>
</table>
== Function ==
[https://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.[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> 
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5zbq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Lysozyme 3D structures|Lysozyme 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Enterobacteria phage RB55]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Han S]]
[[Category: Wu B]]
[[Category: Yang Z]]
[[Category: Zhao Q]]