1hp7: Difference between revisions

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-[[Image:1hp7.gif|left|200px]]<br />
-<applet load="1hp7" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1hp7, resolution 2.1&Aring;" />
-'''A 2.1 ANGSTROM STRUCTURE OF AN UNCLEAVED ALPHA-1-ANTITRYPSIN SHOWS VARIABILITY OF THE REACTIVE CENTER AND OTHER LOOPS'''<br />
-==Overview==
+==A 2.1 ANGSTROM STRUCTURE OF AN UNCLEAVED ALPHA-1-ANTITRYPSIN SHOWS VARIABILITY OF THE REACTIVE CENTER AND OTHER LOOPS==
-Serpin (serine protease inhibitor) proteins are involved in diverse, physiological processes including inflammation, coagulation, matrix, remodeling, and cell differentiation. Deficiency of normal serpin, functions leads to various hereditary diseases. Besides their clinical, importance, serpin proteins draw much attention due to the large, conformational changes that occur upon interaction with proteases. We, present here the crystal structure of an uncleaved alpha(1)-antitrypsin, determined by the multiple isomorphous replacement method and refined to, 2.1 A resolution. The structure, which is the first active serpin, structure based on experimental phases, reveals novel conformations in the, flexible loops, including the proximal hinge region of the reactive center, loop and the surface cavity region in the central beta-sheet, sheet A. The, determined loop conformation explains the results of recent mutagenesis, studies and provides detailed insights into the protease inhibition, mechanism. The high-resolution structure of active alpha(1)-antitrypsin, also provides evidence for the existence of localized van-der-Waals strain, in the central hydrophobic core.
+<StructureSection load='1hp7' size='340' side='right'caption='[[1hp7]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1hp7]] 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=1HP7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HP7 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]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1hp7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hp7 OCA], [https://pdbe.org/1hp7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hp7 RCSB], [https://www.ebi.ac.uk/pdbsum/1hp7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hp7 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/hp/1hp7_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=1hp7 ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-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]]
+*[[Alpha-1-antitrypsin 3D structures|Alpha-1-antitrypsin 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-HP7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN and BME as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HP7 OCA].
+__TOC__
+</StructureSection>
-==Reference==
-A 2.1 A resolution structure of an uncleaved alpha(1)-antitrypsin shows variability of the reactive center and other loops., Kim S, Woo J, Seo EJ, Yu M, Ryu S, J Mol Biol. 2001 Feb 9;306(1):109-19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11178897 11178897]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Kim, S.J.]]
+[[Category: Kim S-J]]
-[[Category: Ryu, S.E.]]
+[[Category: Ryu S-E]]
-[[Category: Seo, E.J.]]
+[[Category: Seo EJ]]
-[[Category: Woo, J.R.]]
+[[Category: Woo J-R]]
-[[Category: Yu, M.H.]]
+[[Category: Yu M-H]]
-[[Category: BME]]
-[[Category: ZN]]
-[[Category: uncleaved alpha-1-antitrypsin serpin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:20:58 2007''