From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1atu.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:1atu.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1atu| PDB=1atu | SCENE= }} | | {{STRUCTURE_1atu| PDB=1atu | SCENE= }} |
| | | | |
| - | '''UNCLEAVED ALPHA-1-ANTITRYPSIN'''
| + | ===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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8939743}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8939743 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_8939743}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 30: |
Line 34: |
| | [[Category: Serine protease inhibitor]] | | [[Category: Serine protease inhibitor]] |
| | [[Category: Stabilizing mutation]] | | [[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 Mon Jun 30 17:34:57 2008'' |
Revision as of 14:34, 30 June 2008
UNCLEAVED ALPHA-1-ANTITRYPSIN
Template:ABSTRACT PUBMED 8939743
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 Mon Jun 30 17:34:57 2008
