1xy4
From Proteopedia
(New page: 200px<br /><applet load="1xy4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xy4" /> '''NMR strcutre of sst1-selective somatostatin ...) |
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| - | [[Image:1xy4.gif|left|200px]]<br /><applet load="1xy4" size=" | + | [[Image:1xy4.gif|left|200px]]<br /><applet load="1xy4" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xy4" /> | caption="1xy4" /> | ||
'''NMR strcutre of sst1-selective somatostatin (SRIF) analog 1'''<br /> | '''NMR strcutre of sst1-selective somatostatin (SRIF) analog 1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three-dimensional NMR structures of six analogues of somatostatin | + | The three-dimensional NMR structures of six analogues of somatostatin (SRIF) are described. These analogues with the amino acid 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 exhibit potent and highly selective binding to human SRIF subtype 1 receptors (sst(1)). The conformations reveal that the backbones of these analogues have a hairpin-like structure similar to the sst(2)-subtype-selective analogues. This structure serves as a scaffold for retaining a unique arrangement of the side chains of d-Trp(8), IAmp(9), Phe(7), and Phe(11) or m-I-Tyr(11) (m-I-Tyr = mono-iodo-tyrosine). The conformational preferences and results from biological analyses of these analogues(1,2) allow a detailed study of the structure-activity relationship of SRIF. The proposed consensus pharmacophore of the sst(1)-selective analogues requires a unique set of distances between an indole/2-naphthyl ring, an IAmp side chain, and two aromatic rings. This motif is necessary and sufficient to explain the binding affinities of all of the analogues studied and is distinct from the existing models suggested for sst(4) as well as sst(2)/sst(5) selectivity. |
==About this Structure== | ==About this Structure== | ||
| - | 1XY4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 1XY4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XY4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Durrer, L.]] | [[Category: Durrer, L.]] | ||
[[Category: Erchegyi, J.]] | [[Category: Erchegyi, J.]] | ||
| - | [[Category: Grace, C | + | [[Category: Grace, C R.R.]] |
| - | [[Category: Koerber, S | + | [[Category: Koerber, S C.]] |
| - | [[Category: Reubi, J | + | [[Category: Reubi, J C.]] |
[[Category: Riek, R.]] | [[Category: Riek, R.]] | ||
| - | [[Category: Rivier, J | + | [[Category: Rivier, J E.]] |
[[Category: gamma turn]] | [[Category: gamma turn]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:59:51 2008'' |
Revision as of 13:59, 21 February 2008
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NMR strcutre of sst1-selective somatostatin (SRIF) analog 1
Overview
The three-dimensional NMR structures of six analogues of somatostatin (SRIF) are described. These analogues with the amino acid 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 exhibit potent and highly selective binding to human SRIF subtype 1 receptors (sst(1)). The conformations reveal that the backbones of these analogues have a hairpin-like structure similar to the sst(2)-subtype-selective analogues. This structure serves as a scaffold for retaining a unique arrangement of the side chains of d-Trp(8), IAmp(9), Phe(7), and Phe(11) or m-I-Tyr(11) (m-I-Tyr = mono-iodo-tyrosine). The conformational preferences and results from biological analyses of these analogues(1,2) allow a detailed study of the structure-activity relationship of SRIF. The proposed consensus pharmacophore of the sst(1)-selective analogues requires a unique set of distances between an indole/2-naphthyl ring, an IAmp side chain, and two aromatic rings. This motif is necessary and sufficient to explain the binding affinities of all of the analogues studied and is distinct from the existing models suggested for sst(4) as well as sst(2)/sst(5) selectivity.
About this Structure
1XY4 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Somatostatin receptor 1 selective analogues: 4. Three-dimensional consensus structure by NMR., Grace CR, Durrer L, Koerber SC, Erchegyi J, Reubi JC, Rivier JE, Riek R, J Med Chem. 2005 Jan 27;48(2):523-33. PMID:15658866
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