View source for 5ezd


==Crystal structure of a Hepatocyte growth factor activator inhibitor-1 (HAI-1) fragment covering the PKD-like 'internal' domain and Kunitz domain 1==
<StructureSection load='5ezd' size='340' side='right'caption='[[5ezd]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</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'>[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>
== Function ==
[https://www.uniprot.org/uniprot/SPIT1_HUMAN SPIT1_HUMAN] Inhibitor of HGF activator. Also acts as an inhibitor of matriptase (ST14).
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== 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<ref>PMID:27189939</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5ezd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hepatocyte growth factor activator inhibitor|Hepatocyte growth factor activator inhibitor]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Andreasen PA]]
[[Category: Hong Z]]
[[Category: Jensen JK]]
[[Category: Morth JP]]