2glh: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2glh.jpg|left|200px]] | [[Image:2glh.jpg|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_2glh", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
| | or leave the SCENE parameter empty for the default display. | ||
| | --> | ||
{{STRUCTURE_2glh| PDB=2glh | SCENE= }} | |||
}} | |||
'''Solution Conformation of Salmon Calcitonin in Sodium Dodecyl Sulfate Micelles''' | '''Solution Conformation of Salmon Calcitonin in Sodium Dodecyl Sulfate Micelles''' | ||
| Line 19: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
2GLH is a [[Single protein]] structure | 2GLH is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GLH OCA]. | ||
==Reference== | ==Reference== | ||
| Line 30: | Line 27: | ||
[[Category: Motta, A.]] | [[Category: Motta, A.]] | ||
[[Category: Nakamuta, H.]] | [[Category: Nakamuta, H.]] | ||
[[Category: | [[Category: A-helix]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:14:24 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 05:14, 4 May 2008
Solution Conformation of Salmon Calcitonin in Sodium Dodecyl Sulfate Micelles
OverviewOverview
Salmon calcitonin (sCT) forms an amphipathic helix in the region 9-19, with the C-terminal decapeptide interacting with the helix (Amodeo, P., Motta, A., Strazzullo, G., Castiglione Morelli, M. A. (1999) J. Biomol. NMR 13, 161-174). To uncover the structural requirements for the hormone bioactivity, we investigated several sCT analogs. They were designed so as to alter the length of the central helix by removal and/or replacement of flanking residues and by selectively mutating or deleting residues inside the helix. The helix content was assessed by circular dichroism and NMR spectroscopies; the receptor binding affinity in human breast cancer cell line T 47D and the in vivo hypocalcemic activity were also evaluated. In particular, by NMR spectroscopy and molecular dynamics calculations we studied Leu(23),Ala(24)-sCT in which Pro(23) and Arg(24) were replaced by helix inducing residues. Compared with sCT, it assumes a longer amphipathic alpha-helix, with decreased binding affinity and one-fifth of the hypocalcemic activity, therefore supporting the idea of a relationship between a definite helix length and bioactivity. From the analysis of other sCT mutants, we inferred that the correct helix length is located in the 9-19 region and requires long range interactions and the presence of specific regions of residues within the sequence for high binding affinity and hypocalcemic activity. Taken together, the structural and biological data identify well defined structural parameters of the helix for sCT bioactivity.
About this StructureAbout this Structure
2GLH is a Single protein structure. Full crystallographic information is available from OCA.
ReferenceReference
Structural determinants of salmon calcitonin bioactivity: the role of the Leu-based amphipathic alpha-helix., Andreotti G, Mendez BL, Amodeo P, Morelli MA, Nakamuta H, Motta A, J Biol Chem. 2006 Aug 25;281(34):24193-203. Epub 2006 Jun 9. PMID:16766525 Page seeded by OCA on Sun May 4 05:14:24 2008