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| - | [[Image:1qmn.gif|left|200px]] | |
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| - | <!-- | + | ==Alpha1-antichymotrypsin serpin in the delta conformation (partial loop insertion)== |
| - | The line below this paragraph, containing "STRUCTURE_1qmn", creates the "Structure Box" on the page.
| + | <StructureSection load='1qmn' size='340' side='right'caption='[[1qmn]], [[Resolution|resolution]] 2.27Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet) | + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1qmn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QMN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QMN FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.27Å</td></tr> |
| - | --> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qmn OCA], [https://pdbe.org/1qmn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qmn RCSB], [https://www.ebi.ac.uk/pdbsum/1qmn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qmn ProSAT]</span></td></tr> |
| - | {{STRUCTURE_1qmn| PDB=1qmn | SCENE= }}
| + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/AACT_HUMAN AACT_HUMAN] Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.<ref>PMID:2404007</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qm/1qmn_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1qmn ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | 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. |
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| - | '''ALPHA1-ANTICHYMOTRYPSIN SERPIN IN THE DELTA CONFORMATION (PARTIAL LOOP INSERTION)'''
| + | 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<ref>PMID:10618372</ref> |
| - | | + | |
| - | | + | |
| - | ==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==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1QMN is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QMN OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1qmn" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | 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:[http://www.ncbi.nlm.nih.gov/pubmed/10618372 10618372]
| + | *[[Serpin 3D structures|Serpin 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Gooptu, B.]] | + | [[Category: Gooptu B]] |
| - | [[Category: Hazes, B.]] | + | [[Category: Hazes B]] |
| - | [[Category: Lomas, D A.]] | + | [[Category: Lomas DA]] |
| - | [[Category: Acute phase protein]]
| + | |
| - | [[Category: Conformational disease]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Emphysema]]
| + | |
| - | [[Category: Loop-sheet polymerization]]
| + | |
| - | [[Category: Partial loop insertion]]
| + | |
| - | [[Category: Serine proteinase inhibitor]]
| + | |
| - | [[Category: Serpin]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:27:18 2008''
| + | |
| Structural highlights
Function
AACT_HUMAN Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rubin H, Wang ZM, Nickbarg EB, McLarney S, Naidoo N, Schoenberger OL, Johnson JL, Cooperman BS. Cloning, expression, purification, and biological activity of recombinant native and variant human alpha 1-antichymotrypsins. J Biol Chem. 1990 Jan 15;265(2):1199-207. PMID:2404007
- ↑ Gooptu B, Hazes B, Chang WS, Dafforn TR, Carrell RW, Read RJ, Lomas DA. Inactive conformation of the serpin alpha(1)-antichymotrypsin indicates two-stage insertion of the reactive loop: implications for inhibitory function and conformational disease. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):67-72. PMID:10618372
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