1g0v
From Proteopedia
(New page: 200px<br /><applet load="1g0v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g0v, resolution 2.00Å" /> '''THE STRUCTURE OF PRO...) |
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| - | [[Image:1g0v.jpg|left|200px]]<br /><applet load="1g0v" size=" | + | [[Image:1g0v.jpg|left|200px]]<br /><applet load="1g0v" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1g0v, resolution 2.00Å" /> | caption="1g0v, resolution 2.00Å" /> | ||
'''THE STRUCTURE OF PROTEINASE A COMPLEXED WITH A IA3 MUTANT, MVV'''<br /> | '''THE STRUCTURE OF PROTEINASE A COMPLEXED WITH A IA3 MUTANT, MVV'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The yeast IA3 polypeptide consists of only 68 residues, and the free | + | The yeast IA3 polypeptide consists of only 68 residues, and the free inhibitor has little intrinsic secondary structure. IA3 showed subnanomolar potency toward its target, proteinase A from Saccharomyces cerevisiae, and did not inhibit any of a large number of aspartic proteinases with similar sequences/structures from a wide variety of other species. Systematic truncation and mutagenesis of the IA3 polypeptide revealed that the inhibitory activity is located in the N-terminal half of the sequence. Crystal structures of different forms of IA3 complexed with proteinase A showed that residues in the N-terminal half of the IA3 sequence became ordered and formed an almost perfect alpha-helix in the active site of the enzyme. This potent, specific interaction was directed primarily by hydrophobic interactions made by three key features in the inhibitory sequence. Whereas IA3 was cut as a substrate by the nontarget aspartic proteinases, it was not cleaved by proteinase A. The random coil IA3 polypeptide escapes cleavage by being stabilized in a helical conformation upon interaction with the active site of proteinase A. This results, paradoxically, in potent selective inhibition of the target enzyme. |
==About this Structure== | ==About this Structure== | ||
| - | 1G0V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with MAN and NAG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Saccharopepsin Saccharopepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.25 3.4.23.25] Full crystallographic information is available from [http:// | + | 1G0V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=MAN:'>MAN</scene> and <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Saccharopepsin Saccharopepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.25 3.4.23.25] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G0V OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Saccharopepsin]] | [[Category: Saccharopepsin]] | ||
| - | [[Category: Brownsey, B | + | [[Category: Brownsey, B G.]] |
[[Category: Bur, D.]] | [[Category: Bur, D.]] | ||
[[Category: Copeland, T.]] | [[Category: Copeland, T.]] | ||
| - | [[Category: Dunn, B | + | [[Category: Dunn, B M.]] |
[[Category: Gustchina, A.]] | [[Category: Gustchina, A.]] | ||
[[Category: Kay, J.]] | [[Category: Kay, J.]] | ||
[[Category: Lees, W.]] | [[Category: Lees, W.]] | ||
[[Category: Li, M.]] | [[Category: Li, M.]] | ||
| - | [[Category: Phylip, L | + | [[Category: Phylip, L H.]] |
[[Category: Winther, J.]] | [[Category: Winther, J.]] | ||
[[Category: Wlodawer, A.]] | [[Category: Wlodawer, A.]] | ||
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[[Category: proteinase a]] | [[Category: proteinase a]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:44:47 2008'' |
Revision as of 10:44, 21 February 2008
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THE STRUCTURE OF PROTEINASE A COMPLEXED WITH A IA3 MUTANT, MVV
Overview
The yeast IA3 polypeptide consists of only 68 residues, and the free inhibitor has little intrinsic secondary structure. IA3 showed subnanomolar potency toward its target, proteinase A from Saccharomyces cerevisiae, and did not inhibit any of a large number of aspartic proteinases with similar sequences/structures from a wide variety of other species. Systematic truncation and mutagenesis of the IA3 polypeptide revealed that the inhibitory activity is located in the N-terminal half of the sequence. Crystal structures of different forms of IA3 complexed with proteinase A showed that residues in the N-terminal half of the IA3 sequence became ordered and formed an almost perfect alpha-helix in the active site of the enzyme. This potent, specific interaction was directed primarily by hydrophobic interactions made by three key features in the inhibitory sequence. Whereas IA3 was cut as a substrate by the nontarget aspartic proteinases, it was not cleaved by proteinase A. The random coil IA3 polypeptide escapes cleavage by being stabilized in a helical conformation upon interaction with the active site of proteinase A. This results, paradoxically, in potent selective inhibition of the target enzyme.
About this Structure
1G0V is a Protein complex structure of sequences from Saccharomyces cerevisiae with and as ligands. Active as Saccharopepsin, with EC number 3.4.23.25 Full crystallographic information is available from OCA.
Reference
The potency and specificity of the interaction between the IA3 inhibitor and its target aspartic proteinase from Saccharomyces cerevisiae., Phylip LH, Lees WE, Brownsey BG, Bur D, Dunn BM, Winther JR, Gustchina A, Li M, Copeland T, Wlodawer A, Kay J, J Biol Chem. 2001 Jan 19;276(3):2023-30. Epub 2000 Oct 19. PMID:11042188
Page seeded by OCA on Thu Feb 21 12:44:47 2008
Categories: Protein complex | Saccharomyces cerevisiae | Saccharopepsin | Brownsey, B G. | Bur, D. | Copeland, T. | Dunn, B M. | Gustchina, A. | Kay, J. | Lees, W. | Li, M. | Phylip, L H. | Winther, J. | Wlodawer, A. | MAN | NAG | Mvv | Proteinase a
