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1go9

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(New page: 200px<br /><applet load="1go9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1go9" /> '''MONITORING THE STRUCTURAL CONSEQUENCES OF PH...)
Current revision (11:23, 27 March 2024) (edit) (undo)
 
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[[Image:1go9.gif|left|200px]]<br /><applet load="1go9" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1go9" />
 
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'''MONITORING THE STRUCTURAL CONSEQUENCES OF PHE12-->D-PHE12 AND LEU15-->AIB15 SUBSTITUTION IN H/R CORTICOTROPIN RELEASING HORMONE: IMPLICATIONS FOR DESIGN OF CRH ANTAGONISTS.'''<br />
 
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==Overview==
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==Monitoring the structural Consequences of Phe12-->D-Phe12 and Leu15-->Aib15 substitution in h/r Corticotropin Releasing Hormone: Implications for Design of CRH antagonists.==
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A new human/rat CRH analogue has been synthesized using the Fmoc/tBu, solid-phase synthetic protocol. The sequence of the new peptide differs, from the original in two positions, 12 and 15, at which the native amino, acids l-phenylalanine 12 and l-leucine 15 have been replaced by the, nonprotein amino acids d-phenylalanine and alpha-aminoisobutyric acid, (Aib), respectively. The high resolution three-dimensional solution, structure of [d-Phe12, Aib15]CRH has been determined by 688 distance, constraints (656 meaningful NOE and 32 H-bonds distance limits) and 21, angle constraints. A family of 40 energy-minimized conformers was obtained, with average rmsd of 0.39 +/- 0.16 A and 0.99 +/- 0.13 A for backbone and, heavy atoms, respectively, and distance penalty functions of 0.42 +/- 0.03, A2. The NMR data acquired in a solvent system of water/trifluoroethanol, (34%/66%, v/v) revealed that this 41-polypeptide adopts an almost linear, helical structure in solution with helical content which reaches an 84% of, the residues. Structural analysis confirmed the existence of two helical, peptide fragments. The first was comprised of residues Ile6-Arg16 and the, second of residues Glu20-Ile40, forming an angle of 34.2 degrees. The, structural differences with respect to the native peptide have been, identified in the region d-Phe12-Glu20 where double substitution at, positions 12 and 15 seems to perturb the elements of the native 35-residue, helix. These structural rearrangements promote non-native intramolecular, interactions in the region of the molecule between either the hydrophobic, side-chains of d-Phe12, Aib15 and Leu18, or the charged groups of the, residue pairs Arg16-Glu20 and His13-Glu17 being responsible for changes in, hormonal functionality. This CRH analogue currently exhibits lack of any, activity.
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<StructureSection load='1go9' size='340' side='right'caption='[[1go9]]' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1go9]] 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=1GO9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GO9 FirstGlance]. <br>
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1GO9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GO9 OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1go9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1go9 OCA], [https://pdbe.org/1go9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1go9 RCSB], [https://www.ebi.ac.uk/pdbsum/1go9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1go9 ProSAT]</span></td></tr>
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Monitoring the structural consequences of Phe12--&gt;D-Phe and Leu15--&gt;Aib substitution in human/rat corticotropin releasing hormone. Implications for design of CRH antagonists., Spyroulias GA, Papazacharias S, Pairas G, Cordopatis P, Eur J Biochem. 2002 Dec;269(24):6009-19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12473096 12473096]
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</table>
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[[Category: Single protein]]
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== Function ==
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[[Category: Cordopatis, P.]]
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[https://www.uniprot.org/uniprot/CRF_HUMAN CRF_HUMAN] This hormone from hypothalamus regulates the release of corticotropin from pituitary gland.
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[[Category: Pairas, G.]]
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== Evolutionary Conservation ==
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[[Category: Papazacharias, S.]]
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[[Image:Consurf_key_small.gif|200px|right]]
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[[Category: Spyroulias, G.A.]]
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Check<jmol>
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[[Category: NH2]]
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<jmolCheckbox>
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[[Category: corticotropin releasing hormone]]
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/go/1go9_consurf.spt"</scriptWhenChecked>
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[[Category: nmr]]
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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[[Category: solid phase synthesis]]
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<text>to colour the structure by Evolutionary Conservation</text>
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[[Category: solutions structure]]
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</jmolCheckbox>
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[[Category: synthetic analogues]]
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</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=1go9 ConSurf].
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<div style="clear:both"></div>
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 01:36:53 2007''
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Cordopatis P]]
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[[Category: Pairas G]]
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[[Category: Papazacharias S]]
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[[Category: Spyroulias GA]]

Current revision

Monitoring the structural Consequences of Phe12-->D-Phe12 and Leu15-->Aib15 substitution in h/r Corticotropin Releasing Hormone: Implications for Design of CRH antagonists.

PDB ID 1go9

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