|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2r0l' size='340' side='right'caption='[[2r0l]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='2r0l' size='340' side='right'caption='[[2r0l]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2r0l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R0L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2r0l]] is a 4 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=2R0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R0L FirstGlance]. <br> |
| - | </td></tr><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ybw|1ybw]], [[1yc0|1yc0]], [[2r0k|2r0k]]</div></td></tr> | + | <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> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HGFAC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2r0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r0l OCA], [https://pdbe.org/2r0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r0l RCSB], [https://www.ebi.ac.uk/pdbsum/2r0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r0l ProSAT]</span></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=2r0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r0l OCA], [https://pdbe.org/2r0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r0l RCSB], [https://www.ebi.ac.uk/pdbsum/2r0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r0l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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.
| + | [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]] |
| Line 39: |
Line 38: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Eigenbrot, C]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Shia, S]] | + | [[Category: Eigenbrot C]] |
| - | [[Category: Allosteric inhibitor]] | + | [[Category: Shia S]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Egf-like domain]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Kringle]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Zymogen]]
| + | |
| 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
To better understand how the relatively flat antigen-combining sites of antibodies interact with the concave shaped substrate-binding clefts of proteases, we determined the structures of two antibodies in complex with the trypsin-like hepatocyte growth-factor activator (HGFA). The two inhibitory antibodies, Ab58 and Ab75, were generated from a human Fab phage display library with synthetic diversity in the three complementarity determining regions (H1, H2, and H3) of the heavy chain, mimicking the natural diversity of the human Ig repertoire. Biochemical studies and the structures of the Fab58:HGFA (3.5-A resolution) and the Fab75:HGFA (2.2-A resolution) complexes revealed that Ab58 obstructed substrate access to the active site, whereas Ab75 allosterically inhibited substrate hydrolysis. In both cases, the antibodies interacted with the same protruding element (99-loop), which forms part of the substrate-binding cleft. Ab58 inserted its H1 and H2 loops in the cleft to occupy important substrate interaction sites (S3 and S2). In contrast, Ab75 bound at the backside of the cleft to a region corresponding to thrombin exosite II, which is known to interact with allosteric effector molecules. In agreement with the structural analysis, binding assays with active site inhibitors and enzymatic assays showed that Ab58 is a competitive inhibitor, and Ab75 is a partial competitive inhibitor. These results provide structural insight into antibody-mediated protease inhibition. They suggest that unlike canonical inhibitors, antibodies may preferentially target protruding loops at the rim of the substrate-binding cleft to interfere with the catalytic machinery of proteases without requiring long insertion loops.
Structural insight into distinct mechanisms of protease inhibition by antibodies.,Wu Y, Eigenbrot C, Liang WC, Stawicki S, Shia S, Fan B, Ganesan R, Lipari MT, Kirchhofer D Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19784-9. Epub 2007 Dec 5. PMID:18077410[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wu Y, Eigenbrot C, Liang WC, Stawicki S, Shia S, Fan B, Ganesan R, Lipari MT, Kirchhofer D. Structural insight into distinct mechanisms of protease inhibition by antibodies. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19784-9. Epub 2007 Dec 5. PMID:18077410
|
