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2wub

From Proteopedia

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[[Image:2wub.png|left|200px]]
 
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==Crystal structure of HGFA in complex with the allosteric non- inhibitory antibody Fab40.deltaTrp==
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The line below this paragraph, containing "STRUCTURE_2wub", creates the "Structure Box" on the page.
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<StructureSection load='2wub' size='340' side='right'caption='[[2wub]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2wub]] is a 8 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=2WUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WUB FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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{{STRUCTURE_2wub| PDB=2wub | SCENE= }}
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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=2wub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wub OCA], [https://pdbe.org/2wub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wub RCSB], [https://www.ebi.ac.uk/pdbsum/2wub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wub ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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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/wu/2wub_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=2wub ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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===Crystal structure of HGFA in complex with the allosteric non- inhibitory antibody Fab40.deltaTrp===
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_20004165}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2wub" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 20004165 is the PubMed ID number.
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{{ABSTRACT_PUBMED_20004165}}
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==About this Structure==
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[[2wub]] is a 8 chain structure of [[Monoclonal Antibody]] 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=2WUB OCA].
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==See Also==
==See Also==
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*[[Monoclonal Antibody]]
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[Hepatocyte growth factor activator|Hepatocyte growth factor activator]]
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==Reference==
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*[[3D structures of human antibody|3D structures of human antibody]]
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<ref group="xtra">PMID:020004165</ref><references group="xtra"/>
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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: Eigenbrot, C.]]
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[[Category: Large Structures]]
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[[Category: Ganesan, R.]]
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[[Category: Eigenbrot C]]
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[[Category: Shia, S.]]
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[[Category: Ganesan R]]
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[[Category: Allosteric inhibitor]]
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[[Category: Shia S]]
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[[Category: Antibody]]
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[[Category: Disulfide bond]]
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[[Category: Egf-like domain]]
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[[Category: Fab complex]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Hydrolase immune system complex]]
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[[Category: Hydrolase-immune system complex]]
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[[Category: Kringle]]
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[[Category: Protease]]
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[[Category: Secreted]]
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[[Category: Serine protease]]
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[[Category: Zymogen]]
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Current revision

Crystal structure of HGFA in complex with the allosteric non- inhibitory antibody Fab40.deltaTrp

PDB ID 2wub

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