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1atu
From Proteopedia
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'''UNCLEAVED ALPHA-1-ANTITRYPSIN''' | '''UNCLEAVED ALPHA-1-ANTITRYPSIN''' | ||
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[[Category: Choi, H J.]] | [[Category: Choi, H J.]] | ||
[[Category: Ryu, S E.]] | [[Category: Ryu, S E.]] | ||
| - | [[Category: | + | [[Category: Alpha-1-antitrypsin]] |
| - | [[Category: | + | [[Category: Conformational transition]] |
| - | [[Category: | + | [[Category: Loop flexibility]] |
| - | [[Category: | + | [[Category: Metastability]] |
| - | [[Category: | + | [[Category: Serine protease inhibitor]] |
| - | [[Category: | + | [[Category: Stabilizing mutation]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:41:03 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:41, 2 May 2008
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| 1atu, resolution 2.70Å () | |||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
UNCLEAVED ALPHA-1-ANTITRYPSIN
Overview
BACKGROUND: The protein alpha1-antitrypsin is a prototype member of the serpin (serine protease inhibitor) family and is known to inhibit the activity of neutrophil elastase in the lower respiratory tract. Members of this family undergo a large structural rearrangement upon binding to a target protease, involving cleavage of the reactive-site loop. This loop is then inserted into the main body of the enzyme following the opening of a central beta sheet, leading to stabilization of the structure. Random mutageneses of alpha1-antitrypsin identified various mutations that stabilize the native structure and retard the insertion of the reactive-site loop. Structural studies of these mutations may reveal the mechanism of the conformational change. RESULTS: We have determined the three-dimensional structure of an uncleaved alpha1-antitrypsin with seven such stabilizing mutations (hepta alpha1-antitrypsin) at 2.7 A resolution. From the comparison of the structure with other serpin structures, we found that hepta alpha1-antitrypsin is stabilized due to the release of various strains that exist in native wild type alpha1-antitrypsin, including unfavorable hydrophobic interactions in the central hydrophobic core. The reactive-site loop of hepta alpha1-antitrypsin is an extended strand, different from that of the previously determined structure of another uncleaved alpha1-antitrypsin, and indicates the inherent flexibility of the loop. CONCLUSIONS: The present structural study suggests that the uncleaved alpha1-antitrypsin has many folding defects which can be improved by mutations. These folding defects seem to be utilized in a coordinated fashion in the regulation of the conformational switch of alpha1-antitrypsin. Some of the defects, represented by the Phe51 region and possibly the Met374 and the Thr59 regions, are part of the sheet-opening mechanism.
About this Structure
1ATU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The native strains in the hydrophobic core and flexible reactive loop of a serine protease inhibitor: crystal structure of an uncleaved alpha1-antitrypsin at 2.7 A., Ryu SE, Choi HJ, Kwon KS, Lee KN, Yu MH, Structure. 1996 Oct 15;4(10):1181-92. PMID:8939743 Page seeded by OCA on Fri May 2 10:41:03 2008
