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| | <StructureSection load='5ezd' size='340' side='right'caption='[[5ezd]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='5ezd' size='340' side='right'caption='[[5ezd]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ezd]] 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=5EZD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EZD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ezd]] 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=5EZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EZD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPINT1, HAI1, UNQ223/PRO256 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></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=5ezd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ezd OCA], [http://pdbe.org/5ezd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ezd RCSB], [http://www.ebi.ac.uk/pdbsum/5ezd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ezd 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=5ezd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ezd OCA], [https://pdbe.org/5ezd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ezd RCSB], [https://www.ebi.ac.uk/pdbsum/5ezd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ezd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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/SPIT1_HUMAN SPIT1_HUMAN] Inhibitor of HGF activator. Also acts as an inhibitor of matriptase (ST14). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Andreasen, P A]] | + | [[Category: Andreasen PA]] |
| - | [[Category: Hong, Z]] | + | [[Category: Hong Z]] |
| - | [[Category: Jensen, J K]] | + | [[Category: Jensen JK]] |
| - | [[Category: Morth, J P]] | + | [[Category: Morth JP]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Multidomain]]
| + | |
| - | [[Category: Serine protease inhibitor]]
| + | |
| - | [[Category: Tertiary structure]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Function
SPIT1_HUMAN Inhibitor of HGF activator. Also acts as an inhibitor of matriptase (ST14).
Publication Abstract from PubMed
Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a type-1 transmembrane protein and inhibitor of several serine proteases including hepatocyte growth factor activator and matriptase. The protein is essential for development as knock-out mice die in utero due to placental defects caused by misregulated extracellular proteolysis. HAI-1 contains two Kunitz-type inhibitor domains (Kunitz), which are generally thought of as a functionally self-contained protease inhibitor unit. This is not the case for HAI-1, where our results reveal how interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. Here we present an X-ray crystal structure of a HAI-1 fragment covering the internal domain and Kunitz-1. The structure not only reveals that the previously uncharacterized internal domain is a member of the polycystic kidney disease (PKD) domain family, but also how the two domains engage in interdomain interactions. Supported by solution small-angle X-ray scattering and a combination of site-directed mutagenesis and functional assays, we show that interdomain interactions not only stabilize the fold of the internal domain but also stimulate the inhibitory activity of Kunitz-1. By completing our structural characterization of the previously unknown N-terminal region of HAI-1, we provide new insight into the interplay between tertiary structure and the inhibitory activity of a multidomain protease inhibitor. We propose a previously unseen mechanism by which the association of an auxiliary domain stimulates the inhibitory activity of a Kunitz-type inhibitor i.e. the first structure of an intramolecular interaction between a Kunitz and another domain.
Crystal Structure of a Two-Domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1: Functional Interactions between the Kunitz-Type Inhibitor Domain-1 and the Neighboring Polycystic Kidney Disease-like Domain.,Hong Z, De Meulemeester L, Jacobi A, Pedersen JS, Morth JP, Andreasen PA, Jensen JK J Biol Chem. 2016 May 6. pii: jbc.M115.707240. PMID:27189939[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hong Z, De Meulemeester L, Jacobi A, Pedersen JS, Morth JP, Andreasen PA, Jensen JK. Crystal Structure of a Two-Domain Fragment of Hepatocyte Growth Factor Activator Inhibitor-1: Functional Interactions between the Kunitz-Type Inhibitor Domain-1 and the Neighboring Polycystic Kidney Disease-like Domain. J Biol Chem. 2016 May 6. pii: jbc.M115.707240. PMID:27189939 doi:http://dx.doi.org/10.1074/jbc.M115.707240
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