View source for 4isl


==Crystal Structure of the inactive Matriptase in complex with its inhibitor HAI-1==
<StructureSection load='4isl' size='340' side='right'caption='[[4isl]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4isl]] 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=4ISL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ISL 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]] 2.29&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=4isl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4isl OCA], [https://pdbe.org/4isl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4isl RCSB], [https://www.ebi.ac.uk/pdbsum/4isl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4isl 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).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Matriptase, a type II trans-membrane serine protease of the S1 trypsin-like family, is expressed on the surface of nearly all normal human epithelium and found in biological fluid-like human milk. Matriptase overexpression has been implicated in tumor progression in certain epithelium-derived cancer cells. Matriptase is tightly regulated by its cognate inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1). It has been demonstrated that the Kunitz domain I (KD1) but not Kunitz domain II (KD2) of HAI-1 is responsible for the inhibitory activity of HAI-1 against matriptase. To investigate the molecular basis of inhibition of matriptase by HAI-1, we solved several crystal structures of matriptase serine protease domain in complex with the fragments of HAI-1. Based on these structures, we found that the binding of KD1 was different from previously predicted binding mode. The P3 arginine residue occupies the S3 specificity pocket of matriptase, but not the S4 pocket as in the cases of hepatocyte growth factor activator.HAI-1 KD1 and matriptase.sunflower trypsin inhibitor-1 complexes. The long 60-loop of matriptase makes direct contact with HAI-1 but remains flexible even in the complexes, and its apex does not bind with KD1 tightly. The interactions between this unique 60-loop and KD1 may provide an opportunity to increase the specificity and inhibitory activity of KD1 for matriptase. Furthermore, comparison between KD1 and a homology model of HAI-1 KD2 rationalizes the structural basis of why KD1 but not KD2 is responsible for the inhibitory activity of HAI-1 against matriptase.

Crystal structures of matriptase in complex with its inhibitor hepatocyte growth factor activator inhibitor-1.,Zhao B, Yuan C, Li R, Qu D, Huang M, Ngo JC J Biol Chem. 2013 Apr 19;288(16):11155-64. doi: 10.1074/jbc.M113.454611. Epub, 2013 Feb 26. PMID:23443661<ref>PMID:23443661</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4isl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hepatocyte growth factor activator inhibitor|Hepatocyte growth factor activator inhibitor]]
*[[Matriptase 3D structures|Matriptase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Huang MD]]
[[Category: Li R]]
[[Category: Yuan C]]
[[Category: Zhao BY]]