1go9 | pdb_00001go9

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

spinqualitylabelsall models 1go9, 1 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1go9 is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: AIB, DPN, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CRF_HUMAN] This hormone from hypothalamus regulates the release of corticotropin from pituitary gland. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. 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from the original in two positions, 12 and 15, at which the native amino acids l-phenylalanine 12 and l-leucine 15 have been replaced by the nonprotein amino acids d-phenylalanine and alpha-aminoisobutyric acid (Aib), respectively.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-->D-Phe and Leu15-->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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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