7s3o

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==NMR Solution Structure of hGal(2-12)KK, a solubility-tagged truncation of the human neuropeptide galanin==
==NMR Solution Structure of hGal(2-12)KK, a solubility-tagged truncation of the human neuropeptide galanin==
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<StructureSection load='7s3o' size='340' side='right'caption='[[7s3o]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''>
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<StructureSection load='7s3o' size='340' side='right'caption='[[7s3o]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7s3o]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S3O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S3O FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7s3o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S3O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S3O FirstGlance]. <br>
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</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>
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</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'>[https://proteopedia.org/fgij/fg.htm?mol=7s3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s3o OCA], [https://pdbe.org/7s3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s3o RCSB], [https://www.ebi.ac.uk/pdbsum/7s3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s3o 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=7s3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s3o OCA], [https://pdbe.org/7s3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s3o RCSB], [https://www.ebi.ac.uk/pdbsum/7s3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s3o ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[https://www.uniprot.org/uniprot/GALA_HUMAN GALA_HUMAN]] The disease is caused by variants affecting the gene represented in this entry.
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[[https://www.uniprot.org/uniprot/GALA_HUMAN GALA_HUMAN]] The disease is caused by variants affecting the gene represented in this entry.
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/GALA_HUMAN GALA_HUMAN]] Endocrine hormone of the central and peripheral nervous systems that binds and activates the G protein-coupled receptors GALR1, GALR2, and GALR3. This small neuropeptide may regulate diverse physiologic functions including contraction of smooth muscle of the gastrointestinal and genitourinary tract, growth hormone and insulin release and adrenal secretion.<ref>PMID:1370155</ref> <ref>PMID:1722333</ref> <ref>PMID:25691535</ref>
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[[https://www.uniprot.org/uniprot/GALA_HUMAN GALA_HUMAN]] Endocrine hormone of the central and peripheral nervous systems that binds and activates the G protein-coupled receptors GALR1, GALR2, and GALR3. This small neuropeptide may regulate diverse physiologic functions including contraction of smooth muscle of the gastrointestinal and genitourinary tract, growth hormone and insulin release and adrenal secretion.<ref>PMID:1370155</ref> <ref>PMID:1722333</ref> <ref>PMID:25691535</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The neuropeptide galanin has a 35-year history as an intriguing target in drug design owing to its implication as a potential anticonvulsant and neuronal trophic factor among many other therapeutically interesting functions including analgesia and mood alteration. In this study, we report the structural characterization of three synthetic fragments of the galanin N-terminus in buffered aqueous solution: hGal(2-12)KK, hGal(1-12)KK, and hGal(1-17)KK. High-field two-dimensional (1)H-(1)H nuclear magnetic resonance (NMR) data were acquired for these fragments and used to derive distance restraints. We further utilized modified hydrogen bonding and dihedral restraints to reflect chemical shift patterns in the data, which revealed the signature of a weakly folded helix. Together, these sets of restraints were used to generate NMR structures of all three fragments, which depict a core of hydrophobic residues that cluster together regardless of the presence of a helical structure, and correspond to residues in the N-terminus of galanin that have been previously shown to be critical for binding its receptors. The helical structure only appears following the inclusion of Gly(1) in the sequence, and at longer sequence lengths, unlike many other peptides, the helix does not propagate. Rather, a few turns of poorly ordered helix appear to be a secondary consequence of clusters of hydrophobic sidechains that are conserved across all of the peptides in this study; the helices themselves appear ordered as a consequence of this clustering, and these clusters compare directly to those observed recently to make contacts between galanin and two of its receptor subtypes. Collapsed hydrophobic residues therefore organize and compose the functional core of human galanin and raise interesting questions about the nature of the conformational order in ligands that bind cell surface receptors.
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Minimal Increments of Hydrophobic Collapse within the N-Terminus of the Neuropeptide Galanin.,Kraichely KN, Clinkscales SE, Hendy CM, Mendoza EA, Parnham S, Giuliano MW Biochemistry. 2022 Jun 21;61(12):1151-1166. doi: 10.1021/acs.biochem.2c00141., Epub 2022 May 27. PMID:35622960<ref>PMID:35622960</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7s3o" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Clinkscales, S E]]
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[[Category: Clinkscales SE]]
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[[Category: Giuliano, M W]]
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[[Category: Giuliano MW]]
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[[Category: Kraichely, K N]]
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[[Category: Kraichely KN]]
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[[Category: Parnham, S]]
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[[Category: Parnham S]]
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[[Category: Binding epitope]]
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[[Category: Neuropeptide]]
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[[Category: Synthetic peptide]]
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Current revision

NMR Solution Structure of hGal(2-12)KK, a solubility-tagged truncation of the human neuropeptide galanin

PDB ID 7s3o

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