This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
4nzl
From Proteopedia
(Difference between revisions)
m (Protected "4nzl" [edit=sysop:move=sysop]) |
|||
| (8 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Extracellular proteins of Staphylococcus aureus inhibit the neutrophil serine proteases== | |
| + | <StructureSection load='4nzl' size='340' side='right'caption='[[4nzl]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4nzl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_Mu50 Staphylococcus aureus subsp. aureus Mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NZL 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]] 1.85Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4nzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nzl OCA], [https://pdbe.org/4nzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nzl RCSB], [https://www.ebi.ac.uk/pdbsum/4nzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nzl ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN] Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM:[https://omim.org/entry/162800 162800]; also known as cyclic neutropenia. CH is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency.<ref>PMID:14673143</ref> <ref>PMID:10581030</ref> Defects in ELANE are the cause of neutropenia severe congenital autosomal dominant type 1 (SCN1) [MIM:[https://omim.org/entry/202700 202700]. SCN1 is a disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.<ref>PMID:20220065</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN] Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.<ref>PMID:15140022</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Neutrophils are indispensable for clearing infections with the prominent human pathogen Staphylococcus aureus. Here, we report that S. aureus secretes a family of proteins that potently inhibits the activity of neutrophil serine proteases (NSPs): neutrophil elastase (NE), proteinase 3, and cathepsin G. The NSPs, but not related serine proteases, are specifically blocked by the extracellular adherence protein (Eap) and the functionally orphan Eap homologs EapH1 and EapH2, with inhibitory-constant values in the low-nanomolar range. Eap proteins are together essential for NSP inhibition by S. aureus in vitro and promote staphylococcal infection in vivo. The crystal structure of the EapH1/NE complex showed that Eap molecules constitute a unique class of noncovalent protease inhibitors that occlude the catalytic cleft of NSPs. These findings increase our insights into the complex pathogenesis of S. aureus infections and create opportunities to design novel treatment strategies for inflammatory conditions related to excessive NSP activity. | ||
| - | + | Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors.,Stapels DA, Ramyar KX, Bischoff M, von Kockritz-Blickwede M, Milder FJ, Ruyken M, Eisenbeis J, McWhorter WJ, Herrmann M, van Kessel KP, Geisbrecht BV, Rooijakkers SH Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13187-92. doi:, 10.1073/pnas.1407616111. Epub 2014 Aug 26. PMID:25161283<ref>PMID:25161283</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4nzl" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Elastase 3D structures|Elastase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Staphylococcus aureus subsp. aureus Mu50]] | ||
| + | [[Category: Bischoff M]] | ||
| + | [[Category: Geisbrecht BV]] | ||
| + | [[Category: Herrmann M]] | ||
| + | [[Category: McWhorter WJ]] | ||
| + | [[Category: Milder F]] | ||
| + | [[Category: Ramyar KX]] | ||
| + | [[Category: Rooijakkers SHM]] | ||
| + | [[Category: Ruyken M]] | ||
| + | [[Category: Scheepmaker L]] | ||
| + | [[Category: Stapels DAC]] | ||
| + | [[Category: Van Kessel KPM]] | ||
| + | [[Category: Von Koeckritz-Blickwede M]] | ||
Current revision
Extracellular proteins of Staphylococcus aureus inhibit the neutrophil serine proteases
| |||||||||||
