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| | <StructureSection load='1yc0' size='340' side='right'caption='[[1yc0]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='1yc0' size='340' side='right'caption='[[1yc0]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1yc0]] is a 2 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=1YC0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1YC0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1yc0]] is a 2 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=1YC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YC0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.6Å</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]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HGFAC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SPINT1, HAI1 ([http://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=1yc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc0 OCA], [https://pdbe.org/1yc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yc0 RCSB], [https://www.ebi.ac.uk/pdbsum/1yc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yc0 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=1yc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yc0 OCA], [http://pdbe.org/1yc0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yc0 RCSB], [http://www.ebi.ac.uk/pdbsum/1yc0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yc0 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. [[http://www.uniprot.org/uniprot/SPIT1_HUMAN SPIT1_HUMAN]] Inhibitor of HGF activator. Also acts as an inhibitor of matriptase (ST14). | + | [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: Corpuz, R T]] | + | [[Category: Corpuz RT]] |
| - | [[Category: Eigenbrot, C]] | + | [[Category: Eigenbrot C]] |
| - | [[Category: Fan, B]] | + | [[Category: Fan B]] |
| - | [[Category: Kirchhofer, D]] | + | [[Category: Kirchhofer D]] |
| - | [[Category: Lazarus, R A]] | + | [[Category: Lazarus RA]] |
| - | [[Category: Santell, L]] | + | [[Category: Santell L]] |
| - | [[Category: Shia, S]] | + | [[Category: Shia S]] |
| - | [[Category: Stamos, J]] | + | [[Category: Stamos J]] |
| - | [[Category: Wu, J]] | + | [[Category: Wu J]] |
| - | [[Category: Hydrolase-inhibitor complex]]
| + | |
| - | [[Category: Hydrolase/inhibitor]]
| + | |
| 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
Hepatocyte growth factor activator (HGFA) is a serine protease that converts hepatocyte growth factor (HGF) into its active form. When activated HGF binds its cognate receptor Met, cellular signals lead to cell growth, differentiation, and migration, activities which promote tissue regeneration in liver, kidney and skin. Intervention in the conversion of HGF to its active form has the potential to provide therapeutic benefit where HGF/Met activity is associated with tumorigenesis. To help identify ways to moderate HGF/Met effects, we have determined the molecular structure of the protease domain of HGFA. The structure we determined, at 2.7 A resolution, with no pseudo-substrate or inhibitor bound is characterized by an unconventional conformation of key residues in the enzyme active site. In order to find whether this apparently non-enzymatically competent arrangement would persist in the presence of a strongly-interacting inhibitor, we also have determined, at 2.6 A resolution, the X-ray structure of HGFA complexed with the first Kunitz domain (KD1) from the physiological inhibitor hepatocyte growth factor activator inhibitor 1B (HAI-1B). In this complex we observe a rearranged substrate binding cleft that closely mirrors the cleft of other serine proteases, suggesting an extreme conformational dynamism. We also characterize the inhibition of 16 serine proteases by KD1, finding that the previously reported enzyme specificity of the intact extracellular region of HAI-1B resides in KD1 alone. We find that HGFA, matriptase, hepsin, plasma kallikrein and trypsin are potently inhibited, and use the complex structure to rationalize the structural basis of these results.
Conformational lability in serine protease active sites: structures of hepatocyte growth factor activator (HGFA) alone and with the inhibitory domain from HGFA inhibitor-1B.,Shia S, Stamos J, Kirchhofer D, Fan B, Wu J, Corpuz RT, Santell L, Lazarus RA, Eigenbrot C J Mol Biol. 2005 Mar 11;346(5):1335-49. Epub 2005 Jan 28. PMID:15713485[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shia S, Stamos J, Kirchhofer D, Fan B, Wu J, Corpuz RT, Santell L, Lazarus RA, Eigenbrot C. Conformational lability in serine protease active sites: structures of hepatocyte growth factor activator (HGFA) alone and with the inhibitory domain from HGFA inhibitor-1B. J Mol Biol. 2005 Mar 11;346(5):1335-49. Epub 2005 Jan 28. PMID:15713485 doi:10.1016/j.jmb.2004.12.048
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