1sel
From Proteopedia
(New page: 200px<br /><applet load="1sel" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sel, resolution 2.0Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1sel.jpg|left|200px]]<br /><applet load="1sel" size=" | + | [[Image:1sel.jpg|left|200px]]<br /><applet load="1sel" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1sel, resolution 2.0Å" /> | caption="1sel, resolution 2.0Å" /> | ||
'''CRYSTAL STRUCTURE OF SELENOSUBTILISIN AT 2.0-ANGSTROMS RESOLUTION'''<br /> | '''CRYSTAL STRUCTURE OF SELENOSUBTILISIN AT 2.0-ANGSTROMS RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three-dimensional structure of selenosubtilisin, an artificial | + | The three-dimensional structure of selenosubtilisin, an artificial selenoenzyme, has been solved at 2.0-A resolution by the method of molecular replacement. Selenosubtilisin is a chemical derivative of the bacterial serine protease subtilisin in which the catalytically essential serine residue has been replaced with a selenocysteine. Its unique hydrolytic and redox properties reflect the intrinsic chemical reactivity of the selenium prosthetic group. Structural analysis of the modified protein reveals that the selenium moiety is selectively incorporated into the side chain of residue 221 and confirms the seleninic acid oxidation state expected from treatment of the enzyme with hydrogen peroxide prior to crystallization. Although the seleninic acid replaces the essential nucleophile in the enzyme's catalytic triad and introduces a negative charge into the active site, the interaction between His64 and Asp32 is not altered by the modification. Hydrogen bonds from the oxygen atoms of the seleninic acid to His64 and to Asn155 in the oxyanion hole confine the prosthetic group to a single well-defined conformation within the active site. These interactions thus provide a structural basis for understanding the seleninic acid's unusually low pKa, the enzyme's relatively sluggish rate of reaction with thiols, and its much more efficient peroxidase activity. Aside from the active site region, the structure of the protein is essentially the same as that previously reported for native subtilisin Carlsberg, indicating the viability of chemical modification strategies for incorporating site-specific changes into the protein backbone. Comparison of the three-dimensional structures of selenosubtilisin and glutathione peroxidase, an important naturally occurring selenoenzyme, provides the means to evaluate how the function of the selenium prosthetic group varies with molecular context. |
==About this Structure== | ==About this Structure== | ||
| - | 1SEL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1SEL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SEL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hilvert, D.]] | [[Category: Hilvert, D.]] | ||
| - | [[Category: Hogle, J | + | [[Category: Hogle, J M.]] |
[[Category: Syed, R.]] | [[Category: Syed, R.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
[[Category: hydrolase(serine protease)]] | [[Category: hydrolase(serine protease)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:00:40 2008'' |
Revision as of 13:00, 21 February 2008
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CRYSTAL STRUCTURE OF SELENOSUBTILISIN AT 2.0-ANGSTROMS RESOLUTION
Overview
The three-dimensional structure of selenosubtilisin, an artificial selenoenzyme, has been solved at 2.0-A resolution by the method of molecular replacement. Selenosubtilisin is a chemical derivative of the bacterial serine protease subtilisin in which the catalytically essential serine residue has been replaced with a selenocysteine. Its unique hydrolytic and redox properties reflect the intrinsic chemical reactivity of the selenium prosthetic group. Structural analysis of the modified protein reveals that the selenium moiety is selectively incorporated into the side chain of residue 221 and confirms the seleninic acid oxidation state expected from treatment of the enzyme with hydrogen peroxide prior to crystallization. Although the seleninic acid replaces the essential nucleophile in the enzyme's catalytic triad and introduces a negative charge into the active site, the interaction between His64 and Asp32 is not altered by the modification. Hydrogen bonds from the oxygen atoms of the seleninic acid to His64 and to Asn155 in the oxyanion hole confine the prosthetic group to a single well-defined conformation within the active site. These interactions thus provide a structural basis for understanding the seleninic acid's unusually low pKa, the enzyme's relatively sluggish rate of reaction with thiols, and its much more efficient peroxidase activity. Aside from the active site region, the structure of the protein is essentially the same as that previously reported for native subtilisin Carlsberg, indicating the viability of chemical modification strategies for incorporating site-specific changes into the protein backbone. Comparison of the three-dimensional structures of selenosubtilisin and glutathione peroxidase, an important naturally occurring selenoenzyme, provides the means to evaluate how the function of the selenium prosthetic group varies with molecular context.
About this Structure
1SEL is a Single protein structure of sequence from Bacillus subtilis with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of selenosubtilisin at 2.0-A resolution., Syed R, Wu ZP, Hogle JM, Hilvert D, Biochemistry. 1993 Jun 22;32(24):6157-64. PMID:8512925
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