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| | ==DETERMINATION OF THE SOLUTION STRUCTURE OF THE PEPTIDE HORMONE GUANYLIN: OBSERVATION OF A NOVEL FORM OF TOPOLOGICAL STEREOISOMERISM== | | ==DETERMINATION OF THE SOLUTION STRUCTURE OF THE PEPTIDE HORMONE GUANYLIN: OBSERVATION OF A NOVEL FORM OF TOPOLOGICAL STEREOISOMERISM== |
| - | <StructureSection load='1gna' size='340' side='right'caption='[[1gna]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1gna' size='340' side='right'caption='[[1gna]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1gna]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GNA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GNA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1gna]] 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=1GNA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GNA FirstGlance]. <br> |
| - | </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=1gna FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gna OCA], [https://pdbe.org/1gna PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gna RCSB], [https://www.ebi.ac.uk/pdbsum/1gna PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gna ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=1gna FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gna OCA], [https://pdbe.org/1gna PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gna RCSB], [https://www.ebi.ac.uk/pdbsum/1gna PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gna ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GUC2A_HUMAN GUC2A_HUMAN]] Endogenous activator of intestinal guanylate cyclase. It stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins.
| + | [https://www.uniprot.org/uniprot/GUC2A_HUMAN GUC2A_HUMAN] Endogenous activator of intestinal guanylate cyclase. It stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Garcia, K C]] | + | [[Category: Garcia KC]] |
| - | [[Category: Skelton, N J]] | + | [[Category: Skelton NJ]] |
| - | [[Category: Hormone]]
| + | |
| Structural highlights
Function
GUC2A_HUMAN Endogenous activator of intestinal guanylate cyclase. It stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins.
Publication Abstract from PubMed
Guanylin is a 15 amino acid mammalian hormone containing two disulfide bonds. Guanylin shares sequence similarity with the bacterial heat-stable enterotoxin (STa) and is capable of binding to and stimulating the STa guanylyl cyclase receptor. Biologically active peptides have been prepared by two methods: (1) enzymatic treatment of a 99 residue proprotein (denoted proguanylin) expressed in Escherichia coli and (2) solid-phase chemical synthesis. Although both sources yield material that is pure by high-performance liquid chromatography and mass spectrometry, analysis by nuclear magnetic resonance (NMR) indicates that peptides from both sources contain two conformationally distinct species present in a 1:1 ratio. The chemical shift differences between the two species are large, allowing unambiguous sequential NMR assignments to be made for both sets of resonances. Exchange between the two forms was not observed even at 70 degrees C. Structural restraints have been generated from nuclear Overhauser effects and scalar coupling constants and used to calculate structures for both forms using distance geometry and restrained energy minimization. The resulting structures for the first isoform are well defined (root-mean-square deviation from the average structure for backbone atoms of 0.47 A) and adopt a right-handed spiral conformation, similar to that observed for heat stable enterotoxin. The second isoform is less well defined (root-mean-square deviation from the average structure for backbone atoms of 1.07 A) but clearly adopts a very different fold consisting of a left-hand spiral. The differences in structure suggest that the two forms may have very different affinities toward the STa receptor. The observation of such isomerism has important implications for the common practice of introducing multiple disulfide bonds into small peptides to limit conformational flexibility and enhance bioactivity.
Determination of the solution structure of the peptide hormone guanylin: observation of a novel form of topological stereoisomerism.,Skelton NJ, Garcia KC, Goeddel DV, Quan C, Burnier JP Biochemistry. 1994 Nov 22;33(46):13581-92. PMID:7947768[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Skelton NJ, Garcia KC, Goeddel DV, Quan C, Burnier JP. Determination of the solution structure of the peptide hormone guanylin: observation of a novel form of topological stereoisomerism. Biochemistry. 1994 Nov 22;33(46):13581-92. PMID:7947768
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