1gd4
From Proteopedia
(New page: 200px<br /> <applet load="1gd4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gd4" /> '''SOLUTION STRUCTURE OF P25S CYSTATIN A'''<br...) |
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| - | [[Image:1gd4.gif|left|200px]]<br /> | + | [[Image:1gd4.gif|left|200px]]<br /><applet load="1gd4" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1gd4" size=" | + | |
caption="1gd4" /> | caption="1gd4" /> | ||
'''SOLUTION STRUCTURE OF P25S CYSTATIN A'''<br /> | '''SOLUTION STRUCTURE OF P25S CYSTATIN A'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The effect of substituting Pro25, located in the alpha-helical region of | + | The effect of substituting Pro25, located in the alpha-helical region of the cystatin A structure, with Ser has been studied. The structures of wild type and P25S cystatin A were determined by multidimensional NMR spectroscopy under comparable conditions. These two structures were virtually identical, and the alpha-helix between Glu15-Lys30 exists with uninterrupted continuity, with a slight bend at residue 25. In order to characterize the possible substitution effects of Pro25 with Ser on the alpha-helix, the chemical shifts of the amide nitrogens and protons, the generalized order parameters obtained by the analyses of the 15N-1H relaxation data, the amide proton exchange rates, and the NOE networks among the alpha-helical and surrounding residues were carefully compared. None of these parameters indicated any significant static or dynamic structural differences between the alpha-helical regions of the wild-type and P25S cystatin A proteins. We therefore conclude that our previous structure of the wild-type cystatin A, in which the alpha-helix exhibited a sharp kink at Pro25, must be revised. The asymmetric distribution of hydrophobic interactions between the side-chain residues of the alpha-helix and the rolled beta-sheet surface, as revealed by NOEs, may be responsible for the slight bend of the alpha-helix in both variants and for the destabilized hydrogen bonding of the alpha-helical residues that follow Pro25/Ser25, as evidenced by increased amide exchange rates. |
==About this Structure== | ==About this Structure== | ||
| - | 1GD4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1GD4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GD4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: thiol protease inhibitor]] | [[Category: thiol protease inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:48:55 2008'' |
Revision as of 10:48, 21 February 2008
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SOLUTION STRUCTURE OF P25S CYSTATIN A
Overview
The effect of substituting Pro25, located in the alpha-helical region of the cystatin A structure, with Ser has been studied. The structures of wild type and P25S cystatin A were determined by multidimensional NMR spectroscopy under comparable conditions. These two structures were virtually identical, and the alpha-helix between Glu15-Lys30 exists with uninterrupted continuity, with a slight bend at residue 25. In order to characterize the possible substitution effects of Pro25 with Ser on the alpha-helix, the chemical shifts of the amide nitrogens and protons, the generalized order parameters obtained by the analyses of the 15N-1H relaxation data, the amide proton exchange rates, and the NOE networks among the alpha-helical and surrounding residues were carefully compared. None of these parameters indicated any significant static or dynamic structural differences between the alpha-helical regions of the wild-type and P25S cystatin A proteins. We therefore conclude that our previous structure of the wild-type cystatin A, in which the alpha-helix exhibited a sharp kink at Pro25, must be revised. The asymmetric distribution of hydrophobic interactions between the side-chain residues of the alpha-helix and the rolled beta-sheet surface, as revealed by NOEs, may be responsible for the slight bend of the alpha-helix in both variants and for the destabilized hydrogen bonding of the alpha-helical residues that follow Pro25/Ser25, as evidenced by increased amide exchange rates.
About this Structure
1GD4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural comparison between wild-type and P25S human cystatin A by NMR spectroscopy. Does this mutation affect the alpha-helix conformation?, Shimba N, Kariya E, Tate S, Kaji H, Kainosho M, J Struct Funct Genomics. 2000;1(1):26-42. PMID:12836678
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