2rmi
From Proteopedia
(New page: 200px<br /><applet load="2rmi" size="350" color="white" frame="true" align="right" spinBox="true" caption="2rmi" /> '''3D NMR structure of astressin'''<br /> ==Ov...) |
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==Overview== | ==Overview== | ||
| - | The C-terminally amidated CRF antagonist astressin binds to CRF-R1 or | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Riek, R.]] | [[Category: Riek, R.]] | ||
[[Category: Rivier, J.]] | [[Category: Rivier, J.]] | ||
| - | [[Category: Royappa, G | + | [[Category: Royappa, G C.R.]] |
[[Category: astressin]] | [[Category: astressin]] | ||
[[Category: crf antagonist]] | [[Category: crf antagonist]] | ||
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[[Category: urotensins]] | [[Category: urotensins]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:48:29 2008'' |
Revision as of 16:48, 21 February 2008
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3D NMR structure of astressin
Overview
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.
About this Structure
2RMI is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 18:48:29 2008
Categories: Single protein | Cervini, L. | Gulyas, J. | Riek, R. | Rivier, J. | Royappa, G C.R. | Astressin | Crf antagonist | Neuropeptide | Nmr | Urocortins | Urotensins
