7qe9: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''Unreleased structure'''
-The entry 7qe9 is ON HOLD
+==Human cationic trypsin (TRY1) complexed with serine protease inhibitor Kazal type 1 N34S (SPINK1 N34S)==
+<StructureSection load='7qe9' size='340' side='right'caption='[[7qe9]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7qe9]] is a 4 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=7QE9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QE9 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=SO4:SULFATE+ION'>SO4</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=7qe9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qe9 OCA], [https://pdbe.org/7qe9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qe9 RCSB], [https://www.ebi.ac.uk/pdbsum/7qe9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qe9 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/TRY1_HUMAN TRY1_HUMAN] Defects in PRSS1 are a cause of pancreatitis (PCTT) [MIM:[https://omim.org/entry/167800 167800]. A disease characterized by the presence of calculi in pancreatic ducts. It causes severe abdominal pain attacks.<ref>PMID:10930381</ref> <ref>PMID:8841182</ref> <ref>PMID:11866271</ref> <ref>PMID:9322498</ref> <ref>PMID:9633818</ref> <ref>PMID:10381903</ref> <ref>PMID:10204851</ref> <ref>PMID:11073545</ref> <ref>PMID:11788572</ref> <ref>PMID:14695529</ref> <ref>PMID:15776435</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/TRY1_HUMAN TRY1_HUMAN] Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates.<ref>PMID:7945238</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+(1) The serine protease inhibitor Kazal type 1 (SPINK1) inhibits trypsin activity in zymogen granules of pancreatic acinar cells. Several mutations in the SPINK1 gene are associated with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). The most common variant is SPINK1 p.N34S. Although this mutation was identified two decades ago, the mechanism of action has remained elusive. (2) SPINK1 and human cationic trypsin (TRY1) were expressed in E. coli, and inhibitory activities were determined. Crystals of SPINK1-TRY1 complexes were grown by using the hanging-drop method, and phases were solved by molecular replacement. (3) Both SPINK1 variants show similar inhibitory behavior toward TRY1. The crystal structures are almost identical, with minor differences in the mutated loop. Both complexes show an unexpected rotamer conformation of the His63 residue in TRY1, which is a member of the catalytic triad. (4) The SPINK1 p.N34S mutation does not affect the inhibitory behavior or the overall structure of the protein. Therefore, the pathophysiological mechanism of action of the p.N34S variant cannot be explained mechanistically or structurally at the protein level. The observed histidine conformation is part of a mechanism for SPINK1 that can explain the exceptional proteolytic stability of this inhibitor.
-Authors:
+Structural and Biophysical Insights into SPINK1 Bound to Human Cationic Trypsin.,Nagel F, Palm GJ, Geist N, McDonnell TCR, Susemihl A, Girbardt B, Mayerle J, Lerch MM, Lammers M, Delcea M Int J Mol Sci. 2022 Mar 23;23(7):3468. doi: 10.3390/ijms23073468. PMID:35408828<ref>PMID:35408828</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7qe9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Trypsin 3D structures|Trypsin 3D structures]]
+*[[Trypsin inhibitor 3D structures|Trypsin inhibitor 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Delcea M]]
+[[Category: Lammers M]]
+[[Category: Nagel F]]
+[[Category: Palm GJ]]