1d5s

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[[Image:1d5s.gif|left|200px]]<br /><applet load="1d5s" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1d5s, resolution 3.0&Aring;" />
 
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'''CRYSTAL STRUCTURE OF CLEAVED ANTITRYPSIN POLYMER'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF CLEAVED ANTITRYPSIN POLYMER==
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Alpha1-antitrypsin deficiency, which can lead to both emphysema and liver disease, is a result of the accumulation of alpha1-antitrypsin polymers within the hepatocyte. A wealth of biochemical and biophysical data suggests that alpha1-antitrypsin polymers form via insertion of residues from the reactive center loop of one molecule into the beta-sheet of another. However, this long-standing hypothesis has not been confirmed by direct structural evidence. Here, we describe the first crystallographic evidence of a beta-strand linked polymer form of alpha1-antitrypsin: the crystal structure of a cleaved alpha1-antitrypsin polymer.
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<StructureSection load='1d5s' size='340' side='right'caption='[[1d5s]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1d5s]] is a 2 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=1D5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D5S FirstGlance]. <br>
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Known diseases associated with this structure: Emphysema OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107400 107400]], Emphysema-cirrhosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107400 107400]], Hemorrhagic diathesis due to antithrombin Pittsburgh OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107400 107400]], Pulmonary disease, chronic obstructive, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107400 107400]]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1d5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d5s OCA], [https://pdbe.org/1d5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d5s RCSB], [https://www.ebi.ac.uk/pdbsum/1d5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d5s ProSAT]</span></td></tr>
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==About this Structure==
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</table>
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1D5S is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=1D5S OCA].
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== Disease ==
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[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>
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==Reference==
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== Function ==
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Cleaved antitrypsin polymers at atomic resolution., Dunstone MA, Dai W, Whisstock JC, Rossjohn J, Pike RN, Feil SC, Le Bonniec BF, Parker MW, Bottomley SP, Protein Sci. 2000 Feb;9(2):417-20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10716194 10716194]
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d5/1d5s_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1d5s ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Bonneic, B F.Le.]]
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[[Category: Bottomley SP]]
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[[Category: Bottomley, S P.]]
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[[Category: Dai W]]
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[[Category: Dai, W.]]
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[[Category: Dunstone MA]]
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[[Category: Dunstone, M A.]]
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[[Category: Feil SC]]
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[[Category: Feil, S C.]]
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[[Category: Le Bonneic BF]]
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[[Category: Parker, M W.]]
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[[Category: Parker MW]]
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[[Category: Pike, R N.]]
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[[Category: Pike RN]]
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[[Category: Rossjohn, J.]]
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[[Category: Rossjohn J]]
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[[Category: Whisstock, J C.]]
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[[Category: Whisstock JC]]
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[[Category: a beta sheet polymerisation]]
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[[Category: rcl cleavage]]
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[[Category: serpin fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:13:17 2008''
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Current revision

CRYSTAL STRUCTURE OF CLEAVED ANTITRYPSIN POLYMER

PDB ID 1d5s

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