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4nzl

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Revision as of 12:52, 11 August 2016

Extracellular proteins of Staphylococcus aureus inhibit the neutrophil serine proteases

Structural highlights

4nzl is a 2 chain structure with sequence from [1] and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Activity:	Leukocyte elastase, with EC number 3.4.21.37
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ELNE_HUMAN] Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM: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.^[1] ^[2] Defects in ELANE are the cause of neutropenia severe congenital autosomal dominant type 1 (SCN1) [MIM: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.^[3]

Function

[ELNE_HUMAN] Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Duan Z, Li FQ, Wechsler J, Meade-White K, Williams K, Benson KF, Horwitz M. A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia. Mol Cell Biol. 2004 Jan;24(1):58-70. PMID:14673143
↑ Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet. 1999 Dec;23(4):433-6. PMID:10581030 doi:10.1038/70544
↑ Germeshausen M, Zeidler C, Stuhrmann M, Lanciotti M, Ballmaier M, Welte K. Digenic mutations in severe congenital neutropenia. Haematologica. 2010 Jul;95(7):1207-10. doi: 10.3324/haematol.2009.017665. Epub, 2010 Mar 10. PMID:20220065 doi:10.3324/haematol.2009.017665
↑ Tralau T, Meyer-Hoffert U, Schroder JM, Wiedow O. Human leukocyte elastase and cathepsin G are specific inhibitors of C5a-dependent neutrophil enzyme release and chemotaxis. Exp Dermatol. 2004 May;13(5):316-25. PMID:15140022 doi:10.1111/j.0906-6705.2004.00145.x
↑ 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. Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors. 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 doi:http://dx.doi.org/10.1073/pnas.1407616111

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nzl"

@@ Line 1: / Line 1: @@
 ==Extracellular proteins of Staphylococcus aureus inhibit the neutrophil serine proteases==
 <StructureSection load='4nzl' size='340' side='right' caption='[[4nzl]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leukocyte_elastase Leukocyte elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.37 3.4.21.37] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nzl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nzl RCSB], [http://www.ebi.ac.uk/pdbsum/4nzl PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nzl OCA], [http://pdbe.org/4nzl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nzl RCSB], [http://www.ebi.ac.uk/pdbsum/4nzl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nzl ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, 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|Elastase]]
 == References ==
 <references/>

4nzl

From Proteopedia

Revision as of 12:52, 11 August 2016

Extracellular proteins of Staphylococcus aureus inhibit the neutrophil serine proteases

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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