View source for 1iz2


==Interactions causing the kinetic trap in serpin protein folding==
<StructureSection load='1iz2' size='340' side='right'caption='[[1iz2]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1iz2]] 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=1IZ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IZ2 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=Z6W:(5R)-5-[(2R)-2-hydroxynonyl]-beta-D-xylulofuranose'>Z6W</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=1iz2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iz2 OCA], [https://pdbe.org/1iz2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1iz2 RCSB], [https://www.ebi.ac.uk/pdbsum/1iz2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1iz2 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/iz/1iz2_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=1iz2 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Conformational transition is fundamental to the mechanism of functional regulation in proteins, and serpins (serine protease inhibitors) can provide insight into this process. Serpins are metastable in their native forms, and they ordinarily undergo conformational transition to a stable state only when they form a tight complex with target proteases. The metastable native form is thus considered to be a kinetically trapped folding intermediate. We sought to understand the nature of the serpin kinetic trap as a step toward discovering how conformational transition is regulated. We found that mutations of the B/C beta-barrel of native alpha(1)-antitrypsin, a prototypical serpin, allowed conversion of the molecule into a more stable state. A 2.2 A resolution crystal structure of the stable form (PDB code, ) showed that the reactive site loop is inserted into an A beta-sheet, as in the latent plasminogen activator inhibitor-1. Mutational analyses suggest strongly that interactions not found in the final stable form cause the kinetic trap in serpin protein folding.

Interactions causing the kinetic trap in serpin protein folding.,Im H, Woo MS, Hwang KY, Yu MH J Biol Chem. 2002 Nov 29;277(48):46347-54. Epub 2002 Sep 18. PMID:12244055<ref>PMID:12244055</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1iz2" 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: Large Structures]]
[[Category: Hwang KY]]
[[Category: Im H]]
[[Category: Woo M-S]]
[[Category: Yu M-H]]