1psi: Difference between revisions
New page: left|200px<br /> <applet load="1psi" size="450" color="white" frame="true" align="right" spinBox="true" caption="1psi, resolution 2.92Å" /> '''INTACT RECOMBINED A... |
No edit summary |
||
| (20 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==Intact recombined alpha1-antitrypsin mutant PHE 51 to LEU== | ||
The reactive site loop of the serpin family of serine proteinase | <StructureSection load='1psi' size='340' side='right'caption='[[1psi]], [[Resolution|resolution]] 2.92Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1psi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The May 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Serpins'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_5 10.2210/rcsb_pdb/mom_2004_5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PSI FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.92Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SCS:3-(ETHYLDISULFANYL)-L-ALANINE'>SCS</scene></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=1psi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1psi OCA], [https://pdbe.org/1psi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1psi RCSB], [https://www.ebi.ac.uk/pdbsum/1psi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1psi ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/A1AT_HUMAN A1AT_HUMAN] Defects in SERPINA1 are the cause of alpha-1-antitrypsin deficiency (A1ATD) [MIM:[https://omim.org/entry/613490 613490]. A disorder whose most common manifestation is emphysema, which becomes evident by the third to fourth decade. A less common manifestation of the deficiency is liver disease, which occurs in children and adults, and may result in cirrhosis and liver failure. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age.<ref>PMID:1905728</ref> <ref>PMID:2390072</ref> <ref>PMID:2227940</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A1AT_HUMAN A1AT_HUMAN] Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.[:]<ref>PMID:1906855</ref> <ref>PMID:1406456</ref> Short peptide from AAT: reversible chymotrypsin inhibitor. It also inhibits elastase, but not trypsin. Its major physiological function is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE).[:]<ref>PMID:1906855</ref> <ref>PMID:1406456</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/ps/1psi_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=1psi ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The reactive site loop of the serpin family of serine proteinase inhibitors is flexible and can adopt a number of diverse conformations. A 2.9 A resolution structure of alpha 1-antitrypsin-the principal proteinase inhibitor in human plasma-shows the loop in a stable canonical conformation matching that found in all other families of serine proteinase inhibitors. This unexpected finding in the absence of loop insertion into the body of the molecule favours a two-stage mechanism of inhibition and provides a model for the heparin activation of antithrombin. The beta-pleated strand conformation of the loop also accounts for the polymerization of the serpins in disease and for their association with other beta-sheet structures, most notably the beta-amyloid of Alzheimer's disease. | |||
Inhibitory conformation of the reactive loop of alpha 1-antitrypsin.,Elliott PR, Lomas DA, Carrell RW, Abrahams JP Nat Struct Biol. 1996 Aug;3(8):676-81. PMID:8756325<ref>PMID:8756325</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1psi" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Alpha-1-antitrypsin 3D structures|Alpha-1-antitrypsin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | |||
[[Category: RCSB PDB Molecule of the Month]] | |||
[[Category: Serpins]] | [[Category: Serpins]] | ||
[[Category: Abrahams JP]] | |||
[[Category: Abrahams | [[Category: Carrell RW]] | ||
[[Category: Carrell | [[Category: Elliott PR]] | ||
[[Category: Elliott | [[Category: Lomas DA]] | ||
[[Category: Lomas | |||
