4nfe: Difference between revisions
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<StructureSection load='4nfe' size='340' side='right'caption='[[4nfe]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4nfe' size='340' side='right'caption='[[4nfe]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4nfe]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4nfe]] 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=4NFE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NFE FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nfe OCA], [https://pdbe.org/4nfe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nfe RCSB], [https://www.ebi.ac.uk/pdbsum/4nfe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nfe ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/KLK2_HUMAN KLK2_HUMAN] Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Kallikrein|Kallikrein]] | *[[Kallikrein 3D structures|Kallikrein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Brandstetter H]] | |||
[[Category: Brandstetter | [[Category: Goettig P]] | ||
[[Category: Goettig | [[Category: Magdolen V]] | ||
[[Category: Magdolen | [[Category: Skala W]] | ||
[[Category: Skala | |||
Latest revision as of 17:47, 8 November 2023
Structural highlights
FunctionKLK2_HUMAN Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. Publication Abstract from PubMedHuman kallikrein-related peptidase (KLK) 2 is a tryptic serine protease predominantly expressed in prostatic tissue and secreted into prostatic fluid, a major component of seminal fluid. Most likely, it activates and complements chymotryptic KLK3 (prostate-specific antigen) in cleaving seminal clotting proteins, resulting in sperm liquefaction. KLK2 belongs to the "classical" KLKs 1-3, which share an extended 99- or kallikrein loop near their non-primed substrate binding site. Here, we report the 1.9 A crystal structures of two KLK2-small molecule inhibitor complexes. In both structures, discontinuous electron density for the 99-loop indicates that this loop is largely disordered. We provide evidence that the 99-loop is responsible for two biochemical peculiarities of KLK2, i.e. reversible inhibition by micromolar Zn2+ concentrations and permanent inactivation by autocatalytic cleavage. Indeed, several 99-loop mutants of KLK2 displayed an altered susceptibility to Zn2+, which located the Zn2+ binding site at the 99-loop/active site interface. In addition, we identified an autolysis site between residues 95e and 95f in the 99-loop, whose elimination prevented the mature enzyme from limited autolysis and irreversible inactivation. An exhaustive comparison of KLK2 with related structures revealed that in the KLK family, the 99-, 148- and 220-loop exist in open and closed conformations, allowing or preventing substrate access, which extends the concept of conformational selection in trypsin-related proteases. Taken together, our novel biochemical and structural data on KLK2 identify its 99-loop as a key player in activity regulation. Structure-Function Analyses of Human Kallikrein-Related Peptidase 2 Establish the 99-Loop as Master Regulator of Activity.,Skala W, Utzschneider DT, Magdolen V, Debela M, Guo S, Craik CS, Brandstetter H, Goettig P J Biol Chem. 2014 Oct 16. pii: jbc.M114.598201. PMID:25326387[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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