2wuc: Difference between revisions

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-[[Image:2wuc.png|left|200px]]
-{{STRUCTURE_2wuc|  PDB=2wuc  |  SCENE=  }}
+==Crystal structure of HGFA in complex with the allosteric non- inhibitory antibody Fab40.deltaTrp and Ac-KQLR-chloromethylketone==
+<StructureSection load='2wuc' size='340' side='right'caption='[[2wuc]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2wuc]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WUC 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]] 2.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=AR7:AMINO{[(4S)-4-AMINO-5,5-DIHYDROXYPENTYL]AMINO}METHANIMINIUM'>AR7</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=2wuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wuc OCA], [https://pdbe.org/2wuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wuc RCSB], [https://www.ebi.ac.uk/pdbsum/2wuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wuc ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/HGFA_HUMAN HGFA_HUMAN] Activates hepatocyte growth factor (HGF) by converting it from a single chain to a heterodimeric form.
+== 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/wu/2wuc_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=2wuc ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Recent structural studies have outlined the mechanism of protease inhibition by active site-directed antibodies. However, the molecular basis of allosteric inhibition by antibodies has been elusive. Here we report the 2.35 A resolution structure of the trypsin-like serine protease hepatocyte growth factor activator (HGFA) in complex with the allosteric antibody Ab40, a potent inhibitor of HGFA catalytic activity. The antibody binds at the periphery of the substrate binding cleft and imposes a conformational change on the entire 99-loop (chymotrypsinogen numbering). The altered conformation of the 99-loop is incompatible with substrate binding due to the partial collapse of subsite S2 and the reorganization of subsite S4. Remarkably, a single residue deletion of Ab40 abolished inhibition of HGFA activity, commensurate with the reversal of the 99-loop conformation to its "competent" state. The results define an "allosteric switch" mechanism as the basis of protease inhibition by an allosteric antibody.
-===Crystal structure of HGFA in complex with the allosteric non- inhibitory antibody Fab40.deltaTrp and Ac-KQLR-chloromethylketone===
+Unraveling the allosteric mechanism of serine protease inhibition by an antibody.,Ganesan R, Eigenbrot C, Wu Y, Liang WC, Shia S, Lipari MT, Kirchhofer D Structure. 2009 Dec 9;17(12):1614-24. PMID:20004165<ref>PMID:20004165</ref>
-{{ABSTRACT_PUBMED_20004165}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 2wuc" style="background-color:#fffaf0;"></div>
-[[2wuc]] is a 5 chain structure with 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=2WUC OCA].
 ==See Also==
-*[[Antibody|Antibody]]
+*[[Antibody 3D structures|Antibody 3D structures]]
+*[[Hepatocyte growth factor activator|Hepatocyte growth factor activator]]
-==Reference==
+*[[3D structures of human antibody|3D structures of human antibody]]
-<ref group="xtra">PMID:020004165</ref><references group="xtra"/>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Eigenbrot, C.]]
+[[Category: Large Structures]]
-[[Category: Ganesan, R.]]
+[[Category: Synthetic construct]]
-[[Category: Shia, S.]]
+[[Category: Eigenbrot C]]
-[[Category: Allosteric inhibitor]]
+[[Category: Ganesan R]]
-[[Category: Antibody]]
+[[Category: Shia S]]
-[[Category: Egf-like domain]]
-[[Category: Fab complex]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Immune system]]
-[[Category: Kringle]]
-[[Category: Serine protease]]