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| | ==Human mesotrypsin-S39Y complexed with bovine pancreatic trypsin inhibitor (BPTI)== | | ==Human mesotrypsin-S39Y complexed with bovine pancreatic trypsin inhibitor (BPTI)== |
| - | <StructureSection load='4dg4' size='340' side='right' caption='[[4dg4]], [[Resolution|resolution]] 1.40Å' scene=''> | + | <StructureSection load='4dg4' size='340' side='right'caption='[[4dg4]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dg4]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DG4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DG4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dg4]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DG4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2r9p|2r9p]]</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=4dg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dg4 OCA], [https://pdbe.org/4dg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dg4 RCSB], [https://www.ebi.ac.uk/pdbsum/4dg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dg4 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRSS3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dg4 OCA], [http://pdbe.org/4dg4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dg4 RCSB], [http://www.ebi.ac.uk/pdbsum/4dg4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dg4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BPT1_BOVIN BPT1_BOVIN]] Inhibits trypsin, kallikrein, chymotrypsin, and plasmin. | + | [[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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4dg4" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4dg4" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[BPTI 3D structures|BPTI 3D structures]] |
| | + | *[[Trypsin 3D structures|Trypsin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Trypsin]] | + | [[Category: Large Structures]] |
| - | [[Category: Radisky, E S]] | + | [[Category: Radisky ES]] |
| - | [[Category: Salameh, M A]] | + | [[Category: Salameh MA]] |
| - | [[Category: Soares, A S]] | + | [[Category: Soares AS]] |
| - | [[Category: Bpti]]
| + | |
| - | [[Category: Canonical inhibitor]]
| + | |
| - | [[Category: Human mesotrypsin]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| 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]
Publication Abstract from PubMed
Mesotrypsin displays unusual resistance to inhibition by polypeptide trypsin inhibitors and cleaves some such inhibitors as substrates, despite a high degree of conservation with other mammalian trypsins. Substitution of Arg for the generally conserved Gly-193 has been implicated as a critical determinant of the unusual behavior of mesotrypsin toward protein protease inhibitors. Another relatively conserved residue near the trypsin active site, Tyr-39, is substituted by Ser-39 in mesotrypsin. Tyr-39, but not Ser-39, forms a hydrogen bond with the main chain amide nitrogen of the P(4) ' residue of a bound protease inhibitor. To investigate the role of the Tyr-39 H-bond in trypsin-inhibitor interactions, we reciprocally mutated position 39 in mesotrypsin and human cationic trypsin to Tyr-39 and Ser-39, respectively. We assessed inhibition constants and cleavage rates of canonical protease inhibitors bovine pancreatic trypsin inhibitor (BPTI) and the amyloid precursor protein Kunitz protease inhibitor domain by mesotrypsin and cationic trypsin variants, finding that the presence of Ser-39 relative to Tyr-39 results in a 4- to 13-fold poorer binding affinity and a 2- to 18-fold increase in cleavage rate. We also report the crystal structure of the mesotrypsin-S39Y*BPTI complex, in which we observe an H-bond between Tyr-39 OH and BPTI Ile-19 N. Our results indicate that the presence of Ser-39 in mesotrypsin, and corresponding absence of a single H-bond to the inhibitor backbone, makes a small but significant functional contribution to the resistance of mesotrypsin to inhibition and the ability of mesotrypsin to proteolyze inhibitors.
Presence versus absence of hydrogen bond donor Tyr-39 influences interactions of cationic trypsin and mesotrypsin with protein protease inhibitors.,Salameh MA, Soares AS, Alloy A, Radisky ES Protein Sci. 2012 Aug;21(8):1103-12. doi: 10.1002/pro.2097. Epub 2012 Jun 25. PMID:22610453[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
- ↑ Salameh MA, Soares AS, Alloy A, Radisky ES. Presence versus absence of hydrogen bond donor Tyr-39 influences interactions of cationic trypsin and mesotrypsin with protein protease inhibitors. Protein Sci. 2012 Aug;21(8):1103-12. doi: 10.1002/pro.2097. Epub 2012 Jun 25. PMID:22610453 doi:http://dx.doi.org/10.1002/pro.2097
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