|
|
| Line 3: |
Line 3: |
| | <StructureSection load='1h4w' size='340' side='right'caption='[[1h4w]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='1h4w' size='340' side='right'caption='[[1h4w]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1h4w]] is a 1 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=1H4W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1H4W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1h4w]] is a 1 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=1H4W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H4W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 1.7Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=1h4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h4w OCA], [http://pdbe.org/1h4w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1h4w RCSB], [http://www.ebi.ac.uk/pdbsum/1h4w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1h4w 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=1h4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h4w OCA], [https://pdbe.org/1h4w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h4w RCSB], [https://www.ebi.ac.uk/pdbsum/1h4w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h4w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRY3_HUMAN TRY3_HUMAN]] Digestive protease specialized for the degradation of trypsin inhibitors. In the ileum, may be involved in defensin processing, including DEFA5.<ref>PMID:12021776</ref> <ref>PMID:14507909</ref> | + | [https://www.uniprot.org/uniprot/TRY3_HUMAN TRY3_HUMAN] Digestive protease specialized for the degradation of trypsin inhibitors. In the ileum, may be involved in defensin processing, including DEFA5.<ref>PMID:12021776</ref> <ref>PMID:14507909</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 36: |
Line 36: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Trypsin]]
| + | [[Category: Berglund GI]] |
| - | [[Category: Berglund, G I]] | + | [[Category: Graf L]] |
| - | [[Category: Graf, L]] | + | [[Category: Hajdu J]] |
| - | [[Category: Hajdu, J]] | + | [[Category: Katona G]] |
| - | [[Category: Katona, G]] | + | [[Category: Szilagyi L]] |
| - | [[Category: Szilagyi, L]] | + | |
| - | [[Category: Alzheimer disease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibitor resistance]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Signal transduction]]
| + | |
| Structural highlights
Function
TRY3_HUMAN Digestive protease specialized for the degradation of trypsin inhibitors. In the ileum, may be involved in defensin processing, including DEFA5.[1] [2]
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
Severe neurodegradative brain diseases, like Alzheimer, are tightly linked with proteolytic activity in the human brain. Proteinases expressed in the brain, such as human trypsin IV, are likely to be involved in the pathomechanism of these diseases. The observation of amyloid formed in the brain of transgenic mice expressing human trypsin IV supports this hypothesis. Human trypsin IV is also resistant towards all studied naturally occurring polypeptide inhibitors. It has been postulated that the substitution of Gly193 to arginine is responsible for this inhibitor resistance. Here we report the X-ray structure of human trypsin IV in complex with the inhibitor benzamidine at 1.7 A resolution. The overall fold of human trypsin IV is similar to human trypsin I, with a root-mean square deviation of only 0.5 A for all C(alpha) positions. The crystal structure reveals the orientation of the side-chain of Arg193, which occupies an extended conformation and fills the S2' subsite. An analysis of surface electrostatic potentials shows an unusually strong clustering of positive charges around the primary specificity pocket, to which the side-chain of Arg193 also contributes. These unique features of the crystal structure provide a structural basis for the enhanced inhibitor resistance, and enhanced substrate restriction, of human trypsin IV.
Crystal structure reveals basis for the inhibitor resistance of human brain trypsin.,Katona G, Berglund GI, Hajdu J, Graf L, Szilagyi L J Mol Biol. 2002 Feb 1;315(5):1209-18. PMID:11827488[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol. 2002 Jun;3(6):583-90. Epub 2002 May 20. PMID:12021776 doi:10.1038/ni797
- ↑ Szmola R, Kukor Z, Sahin-Toth M. Human mesotrypsin is a unique digestive protease specialized for the degradation of trypsin inhibitors. J Biol Chem. 2003 Dec 5;278(49):48580-9. Epub 2003 Sep 24. PMID:14507909 doi:10.1074/jbc.M310301200
- ↑ Katona G, Berglund GI, Hajdu J, Graf L, Szilagyi L. Crystal structure reveals basis for the inhibitor resistance of human brain trypsin. J Mol Biol. 2002 Feb 1;315(5):1209-18. PMID:11827488 doi:10.1006/jmbi.2001.5305
|
