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| | <StructureSection load='2wuc' size='340' side='right'caption='[[2wuc]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='2wuc' size='340' side='right'caption='[[2wuc]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wuc]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=2WUC FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><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></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ybw|1ybw]], [[1yc0|1yc0]], [[2wub|2wub]]</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> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2wuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wuc OCA], [http://pdbe.org/2wuc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wuc RCSB], [http://www.ebi.ac.uk/pdbsum/2wuc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wuc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HGFA_HUMAN HGFA_HUMAN]] Activates hepatocyte growth factor (HGF) by converting it from a single chain to a heterodimeric form. | + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Eigenbrot, C]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Ganesan, R]] | + | [[Category: Eigenbrot C]] |
| - | [[Category: Shia, S]] | + | [[Category: Ganesan R]] |
| - | [[Category: Allosteric inhibitor]] | + | [[Category: Shia S]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Egf-like domain]]
| + | |
| - | [[Category: Fab complex]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Kringle]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| Structural highlights
Function
HGFA_HUMAN Activates hepatocyte growth factor (HGF) by converting it from a single chain to a heterodimeric form.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ganesan R, Eigenbrot C, Wu Y, Liang WC, Shia S, Lipari MT, Kirchhofer D. Unraveling the allosteric mechanism of serine protease inhibition by an antibody. Structure. 2009 Dec 9;17(12):1614-24. PMID:20004165 doi:10.1016/j.str.2009.09.014
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