|
|
(3 intermediate revisions by the same user not shown) |
Line 1: |
Line 1: |
|
| |
|
| ==[hPP19-23]-pNPY bound to DPC Micelles== | | ==[hPP19-23]-pNPY bound to DPC Micelles== |
| <StructureSection load='1tz4' size='340' side='right' caption='[[1tz4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | | <StructureSection load='1tz4' size='340' side='right'caption='[[1tz4]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1tz4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TZ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TZ4 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1tz4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TZ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TZ4 FirstGlance]. <br> |
| </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1f8p|1f8p]], [[1ljv|1ljv]], [[1tz5|1tz5]]</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=1tz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tz4 OCA], [http://pdbe.org/1tz4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tz4 RCSB], [http://www.ebi.ac.uk/pdbsum/1tz4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tz4 ProSAT]</span></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=1tz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tz4 OCA], [https://pdbe.org/1tz4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tz4 RCSB], [https://www.ebi.ac.uk/pdbsum/1tz4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tz4 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/NPY_PIG NPY_PIG]] NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone. | | [https://www.uniprot.org/uniprot/NPY_PIG NPY_PIG] NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.[https://www.uniprot.org/uniprot/PAHO_HUMAN PAHO_HUMAN] Pancreatic hormone is synthesized in pancreatic islets of Langerhans and acts as a regulator of pancreatic and gastrointestinal functions. The physiological role for the icosapeptide has not yet been elucidated. |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
Line 20: |
Line 20: |
| </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1tz4 ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1tz4 ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| Neuropeptide Y (NPY) and the pancreatic polypeptide (PP) are members of the neuropeptide Y family of hormones. They bind to the Y receptors with very different affinities: Whereas PP is highly selective for the Y(4) receptor, NPY displays highest affinites for Y(1), Y(2), and Y(5) receptor subtypes. Introducing the NPY segment 19-23 into PP leads to an increase in affinity at the Y(1) and Y(2) receptor subtypes whereas the exchange of this segment from PP into NPY leads to a large decrease in affinity at all receptor subtypes. PP displays a very stable structure in solution, with the N terminus being back-folded onto the C-terminal alpha-helix (the so-called PP-fold). The helix of NPY is less stable and the N terminus is freely diffusing in solution. The exchange of this segment, however, does not alter the PP-fold propensities of the chimeric peptides in solution. The structures of the phospholipid micelle-bound peptides serving to mimic the membrane-bound species display segregation into a more flexible N-terminal region and a well-defined alpha-helical region. The introduction of the [19-23]-pNPY segment into hPP leads to an N-terminal extension of the alpha-helix, now starting at Pro(14) instead of Met(17). In contrast, a truncated helix is observed in [(19)(-)(23)hPP]-pNPY, starting at Leu(17) instead of Ala(14). All peptides display moderate binding affinities to neutral membranes (K(assoc) in the range of 1.7 to 6.8 x 10(4) mol(-)(1) as determined by surface plasmon resonance) with the differences in binding being most probably related to the exchange of Arg-19 (pNPY) by Glu-23 (hPP). Differences in receptor binding properties between the chimeras and their parental peptides are therefore most likely due to changes in the conformation of the micelle-bound peptides.
| |
|
| |
| Strongly altered receptor binding properties in PP and NPY chimeras are accompanied by changes in structure and membrane binding.,Lerch M, Kamimori H, Folkers G, Aguilar MI, Beck-Sickinger AG, Zerbe O Biochemistry. 2005 Jun 28;44(25):9255-64. PMID:15966750<ref>PMID:15966750</ref>
| |
|
| |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| |
| </div>
| |
| <div class="pdbe-citations 1tz4" style="background-color:#fffaf0;"></div>
| |
| == References ==
| |
| <references/>
| |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Aguilar, M I]] | | [[Category: Large Structures]] |
| [[Category: Beck-Sickinger, A G]] | | [[Category: Sus scrofa]] |
| [[Category: Folkers, G]] | | [[Category: Aguilar MI]] |
| [[Category: Kamimori, H]] | | [[Category: Beck-Sickinger AG]] |
| [[Category: Lerch, M]] | | [[Category: Folkers G]] |
| [[Category: Zerbe, O]] | | [[Category: Kamimori H]] |
| [[Category: Neuropeptide]] | | [[Category: Lerch M]] |
| [[Category: Npy-pp chimera]] | | [[Category: Zerbe O]] |