1qmn
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1qmn.gif|left|200px]] | [[Image:1qmn.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1qmn", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | | | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | + | --> | |
| - | + | {{STRUCTURE_1qmn| PDB=1qmn | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''ALPHA1-ANTICHYMOTRYPSIN SERPIN IN THE DELTA CONFORMATION (PARTIAL LOOP INSERTION)''' | '''ALPHA1-ANTICHYMOTRYPSIN SERPIN IN THE DELTA CONFORMATION (PARTIAL LOOP INSERTION)''' | ||
| Line 28: | Line 25: | ||
[[Category: Hazes, B.]] | [[Category: Hazes, B.]] | ||
[[Category: Lomas, D A.]] | [[Category: Lomas, D A.]] | ||
| - | [[Category: | + | [[Category: Acute phase protein]] |
| - | [[Category: | + | [[Category: Conformational disease]] |
| - | [[Category: | + | [[Category: Disease mutation]] |
| - | [[Category: | + | [[Category: Emphysema]] |
| - | [[Category: | + | [[Category: Loop-sheet polymerization]] |
| - | [[Category: | + | [[Category: Partial loop insertion]] |
| - | [[Category: | + | [[Category: Serine proteinase inhibitor]] |
| - | [[Category: | + | [[Category: Serpin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:27:18 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 03:27, 3 May 2008
ALPHA1-ANTICHYMOTRYPSIN SERPIN IN THE DELTA CONFORMATION (PARTIAL LOOP INSERTION)
Overview
The serpins are a family of proteinase inhibitors that play a central role in the control of proteolytic cascades. Their inhibitory mechanism depends on the intramolecular insertion of the reactive loop into beta-sheet A after cleavage by the target proteinase. Point mutations within the protein can allow aberrant conformational transitions characterized by beta-strand exchange between the reactive loop of one molecule and beta-sheet A of another. These loop-sheet polymers result in diseases as varied as cirrhosis, emphysema, angio-oedema, and thrombosis, and we recently have shown that they underlie an early-onset dementia. We report here the biochemical characteristics and crystal structure of a naturally occurring variant (Leu-55-Pro) of the plasma serpin alpha(1)-antichymotrypsin trapped as an inactive intermediate. The structure demonstrates a serpin configuration with partial insertion of the reactive loop into beta-sheet A. The lower part of the sheet is filled by the last turn of F-helix and the loop that links it to s3A. This conformation matches that of proposed intermediates on the pathway to complex and polymer formation in the serpins. In particular, this intermediate, along with the latent and polymerized conformations, explains the loss of activity of plasma alpha(1)-antichymotrypsin associated with chronic obstructive pulmonary disease in patients with the Leu-55-Pro mutation.
About this Structure
1QMN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Inactive conformation of the serpin alpha(1)-antichymotrypsin indicates two-stage insertion of the reactive loop: implications for inhibitory function and conformational disease., Gooptu B, Hazes B, Chang WS, Dafforn TR, Carrell RW, Read RJ, Lomas DA, Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):67-72. PMID:10618372 Page seeded by OCA on Sat May 3 06:27:18 2008
