Structural highlights
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
The C-terminally amidated CRF antagonist astressin binds to CRF-R1 or CRF-R2 receptors with low nanomolar affinity while the corresponding astressin-acid has >100 times less affinity. To understand the role of the amide group in binding, the conformations of astressin-amide and astressin-acid were studied in DMSO using NMR techniques. The 3D NMR structures show that the backbones of both analogs prefer an alpha-helical conformation, with a small kink around Gln(26). However, astressin-amide has a well-defined helical structure from Leu(27) to Ile(41) and a conformation very similar to the bioactive conformation reported by our group (Grace et al., Proc Natl Acad Sci USA 2007, 104, 4858-4863). In contrast, astressin-acid has an irregular helical conformation from Arg(35) onward, including a rearrangement of the side chains in that region. This structural difference highlights the crucial role of the C-terminal amidation for stabilization of astressin's bioactive conformation.
Astressin-amide and astressin-acid are structurally different in dimethylsulfoxide.,Grace CR, Cervini L, Gulyas J, Rivier J, Riek R Biopolymers. 2007 Oct 5-15;87(2-3):196-205. PMID:17657708[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Grace CR, Cervini L, Gulyas J, Rivier J, Riek R. Astressin-amide and astressin-acid are structurally different in dimethylsulfoxide. Biopolymers. 2007 Oct 5-15;87(2-3):196-205. PMID:17657708 doi:10.1002/bip.20818