2z7f: Difference between revisions
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==Crystal structure of the complex of human neutrophil elastase with 1/2SLPI== | |||
=== | <StructureSection load='2z7f' size='340' side='right' caption='[[2z7f]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2z7f]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z7F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Z7F FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br> | |||
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2z7f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z7f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2z7f RCSB], [http://www.ebi.ac.uk/pdbsum/2z7f PDBsum]</span></td></tr> | |||
<table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/ELNE_HUMAN ELNE_HUMAN]] Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM:[http://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:[http://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 == | |||
[[http://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> [[http://www.uniprot.org/uniprot/SLPI_HUMAN SLPI_HUMAN]] Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G. May prevent elastase-mediated damage to oral and possibly other mucosal tissues. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z7/2z7f_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
SLPI (secretory leukocyte protease inhibitor) is a 107-residue non-glycosylated protease inhibitor, which inhibits a wide range of serine proteases, trypsin, chymotrypsin, neutrophil elastase, chymase and cathepsin G. X-ray crystallographic analyses have shown that SLPI comprises two separate domains of similar architecture [Grutter, Fendrich, Huber & Bode (1988), EMBO J. 7, 345-351] and the C-terminal domain interacts with bovine alpha-chymotrypsin. In order to understand SLPI's multiple functions against various serine proteases, the complex HNE (human neutrophil elastase) has been co-crystallized with 1/2SLPI (recombinant C-terminal domain of SLPI; Arg58-Ala107), which has a biological activity similar to full SLPI. The 1/2SLPI and HNE complex structure was solved at 1.7 A resolution, and compared with the interaction mechanism of elafin, which is a specific inhibitor of elastase. It was found that P1 Leu72i and six hydrogen bonds between the main chains in the primary contact region have sufficient ability to inhibit HNE and PPE (porcine pancreatic elastase), and P5 Tyr68i is important in increasing the selectivity of 1/2SLPI against HNE. The mechanisms of the functions of SLPI are relatively unknown, but the current study could help understand the selectivity of SLPI against HNE and PPE. | |||
Complex of human neutrophil elastase with 1/2SLPI.,Koizumi M, Fujino A, Fukushima K, Kamimura T, Takimoto-Kamimura M J Synchrotron Radiat. 2008 May;15(Pt 3):308-11. Epub 2008 Apr 18. PMID:18421166<ref>PMID:18421166</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Elastase|Elastase]] | *[[Elastase|Elastase]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Leukocyte elastase]] | [[Category: Leukocyte elastase]] | ||