1goe
From Proteopedia
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|PDB= 1goe |SIZE=350|CAPTION= <scene name='initialview01'>1goe</scene> | |PDB= 1goe |SIZE=350|CAPTION= <scene name='initialview01'>1goe</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=NH2:AMINO GROUP'>NH2</scene> | + | |LIGAND= <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> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1goe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1goe OCA], [http://www.ebi.ac.uk/pdbsum/1goe PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1goe RCSB]</span> | ||
}} | }} | ||
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[[Category: Papazacharias, S.]] | [[Category: Papazacharias, S.]] | ||
[[Category: Spyroulias, G A.]] | [[Category: Spyroulias, G A.]] | ||
| - | [[Category: NH2]] | ||
[[Category: corticotropin releasing hormone]] | [[Category: corticotropin releasing hormone]] | ||
[[Category: nmr]] | [[Category: nmr]] | ||
| Line 32: | Line 34: | ||
[[Category: synthetic analogue]] | [[Category: synthetic analogue]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:48:14 2008'' |
Revision as of 17:48, 30 March 2008
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| Ligands: | , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
MONITORING THE STRUCTURAL CONSEQUENCES OF PHE12-->D-PHE12 AND LEU15-->AIB15 SUBSTITUTION IN H/R CORTICOTROPIN RELEASING HORMONE: IMPLICATIONS FOR DESIGN OF CRH ANTAGONISTS.
Overview
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from the original in two positions, 12 and 15, at which the native amino acids l-phenylalanine 12 and l-leucine 15 have been replaced by the nonprotein amino acids d-phenylalanine and alpha-aminoisobutyric acid (Aib), respectively.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.
About this Structure
1GOE is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
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
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