1goe

<StructureSection load='1goe' size='340' side='right'caption='[[1goe]], [[NMR_Ensembles_of_Models | 40 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[1goe]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GOE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GOE FirstGlance]. <br>

</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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>

[[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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== Publication Abstract from PubMed ==

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from the original in two positions, 12 and 15, at which the native amino acids l-phenylalanine 12 and l-leucine 15 have been replaced by the nonprotein amino acids d-phenylalanine and alpha-aminoisobutyric acid (Aib), respectively.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.

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:12473096<ref>PMID:12473096</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 1goe" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Cordopatis, P]]

[[Category: Pairas, G]]

[[Category: Papazacharias, S]]

[[Category: Spyroulias, G A]]

[[Category: Synthetic analogue]]