View source for 8d7k


==Bifunctional Inhibition of Neutrophil Elastase and Cathepsin G by Eap2 from S. aureus==
<StructureSection load='8d7k' size='340' side='right'caption='[[8d7k]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8d7k]] is a 12 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=8D7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D7K 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]] 3.1&#8491;</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=8d7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d7k OCA], [https://pdbe.org/8d7k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d7k RCSB], [https://www.ebi.ac.uk/pdbsum/8d7k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d7k ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CATG_HUMAN CATG_HUMAN] Serine protease with trypsin- and chymotrypsin-like specificity. Cleaves complement C3. Has antibacterial activity against the Gram-negative bacterium P.aeruginosa, antibacterial activity is inhibited by LPS from P.aeruginosa, Z-Gly-Leu-Phe-CH2Cl and phenylmethylsulfonyl fluoride.<ref>PMID:8194606</ref> <ref>PMID:1861080</ref> <ref>PMID:1937776</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Staphylococcus aureus expresses three high-affinity neutrophil serine protease (NSP) inhibitors known as the extracellular adherence protein domain (EAPs) proteins. Whereas EapH1 and EapH2 are comprised of a single EAP domain, the modular extracellular adherence protein (Eap) from S. aureus strain Mu50 consists of four EAP domains. We recently reported that EapH2 can simultaneously bind and inhibit cathepsin-G (CG) and neutrophil elastase (NE), which are the two most abundant NSPs. This unusual property of EapH2 arises from independent CG and NE-binding sites that lie on opposing faces of its EAP domain. Here we used X-ray crystallography and enzyme assays to show that all four individual domains of Eap (i.e. Eap1, Eap2, Eap3, and Eap4) exhibit an EapH2-like ability to form ternary complexes with CG and NE that inhibit both enzymes simultaneously. We found that Eap1, Eap2, and Eap3 have similar functional profiles insofar as NSP inhibition is concerned but that Eap4 displays an unexpected ability to inhibit two NE enzymes simultaneously. Using X-ray crystallography, we determined that this second NE-binding site in Eap4 arises through the same region of its EAP domain that also comprises its CG-binding site. Interestingly, small angle X-ray scattering data showed that stable tail-to-tail dimers of the NE/Eap4/NE ternary complex exist in solution. This arrangement is compatible with NSP-binding at all available sites in a two-domain fragment of Eap. Together, our work implies that Eap is a polyvalent inhibitor of NSPs. It also raises the possibility that higher-order structures of NSP-bound Eap may have unique functional properties.

S. aureus Eap is a polyvalent inhibitor of neutrophil serine proteases.,Mishra N, Gido CD, Herdendorf TJ, Hammel M, Hura GL, Fu ZQ, Geisbrecht BV J Biol Chem. 2024 Sep;300(9):107627. doi: 10.1016/j.jbc.2024.107627. Epub 2024 , Aug 3. PMID:39098536<ref>PMID:39098536</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8d7k" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Staphylococcus aureus subsp. aureus Mu50]]
[[Category: Geisbrecht BV]]
[[Category: Gido CD]]
[[Category: Herdendorf TJ]]