8d4q
From Proteopedia
(Difference between revisions)
| Line 8: | Line 8: | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8d4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d4q OCA], [https://pdbe.org/8d4q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d4q RCSB], [https://www.ebi.ac.uk/pdbsum/8d4q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d4q ProSAT]</span></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=8d4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d4q OCA], [https://pdbe.org/8d4q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d4q RCSB], [https://www.ebi.ac.uk/pdbsum/8d4q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d4q ProSAT]</span></td></tr> | ||
</table> | </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 == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [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 == | ||
| + | Extracellular adherence protein domain (EAPs) proteins are a class of innate immune evasion proteins secreted by the human pathogen Staphylococcus aureus. EAPs are potent and selective inhibitors of cathepsin-G (CG) and neutrophil elastase (NE), which are the two most abundant neutrophil serine proteases (NSPs). Previous work from our group has shown that the prototypical EAP, EapH1, relies on plasticity within a single inhibitory site to block the activities of CG and NE. However, whether other EAPs follow similar structure-function relationships is unclear. To address this question, we studied the inhibitory properties of the first (Eap1) and second (Eap2) domains of the modular extracellular adherence protein of S. aureus and determined their structures when bound to CG and NE, respectively. We observed that both Eap1 and Eap2 displayed time-dependent inhibition of CG (on the order of 10(-9) M) and of NE (on the order of 10(-10) M). We also found that whereas the structures of Eap1 and Eap2 bound to CG showed an overall inhibitory mode like that seen previously for EapH1, the structures of Eap1 and Eap2 bound to NE revealed a new inhibitory mode involving a distal region of the EAP domain. Using site-directed mutagenesis of Eap1 and Eap2, along with enzyme assays, we confirmed the roles of interfacial residues in NSP inhibition. Taken together, our work demonstrates that EAPs can form structurally divergent complexes with two closely related serine proteases and further suggests that certain EAPs may be capable of inhibiting two NSPs simultaneously. | ||
| + | |||
| + | Characterization of two distinct neutrophil serine protease-binding modes within a Staphylococcus aureus innate immune evasion protein family.,Gido CD, Herdendorf TJ, Geisbrecht BV J Biol Chem. 2023 Mar;299(3):102969. doi: 10.1016/j.jbc.2023.102969. Epub 2023 , Feb 1. PMID:36736422<ref>PMID:36736422</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8d4q" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Elastase 3D structures|Elastase 3D structures]] | *[[Elastase 3D structures|Elastase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal Structure of Neutrophil Elastase Inhibited by Eap1 from S. aureus
| |||||||||||
